Skip to main content
SpringerLink
Log in

Molecular Carcinogenesis in Gynecologic Neoplasias

  • Chapter
  • First Online:
Mechanisms of Molecular Carcinogenesis – Volume 2

  • 686 Accesses

Abstract

Breast cancer is the most common cancer in women worldwide and accounted for 1.7 million new cases in 2012, which is a quarter of all new cases of cancer. In 2014, the American Cancer Society reported 235,030 new cases of breast cancer and 40,430 deaths related to breast cancer. Among women in the United States, breast cancer is the most common malignancy, the second most common cause of death from cancer and a leading cause of premature mortality from cancer in women. Ovarian cancer occurs with a lifetime risk of 1.4% in the general female population, but with a risk of 15–56% in women carrying a germline mutation of the BRCA1 and BRCA2 genes. Epithelial ovarian cancer (EOC) is the leading cause of death among gynecologic cancers in the western world and the fifth leading cause of cancer-related death in women. Worldwide, about 200,000 women are newly diagnosed, with 125,000 disease-related deaths every year. Endometrial cancer is the most common gynecologic cancer in the USA, accounting for 40,100 new cases and 7470 deaths per year. Endometrial cancer shares similar patterns of distribution by age and geography with ovarian cancer.

Overall gynecologic malignancies pose a significant disease burden, and novel therapeutic strategies are needed to decrease morbidity and mortality from gynecological cancer. Understanding the molecular characteristics of gynecological cancer ist crucial to develop new targeted therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ferlay J, Soerjomataram I, Ervik M, Bray FD. International Agency for Research on Cancer; GLOBOCAN 2012: Cancer Incidence, Mortality and Prevalence Worldwide. http://www.globocan.iarc.fr/pages/fact_sheets_cancer.aspx. Accessed 21 Mar 2014.

  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.

    Article  PubMed  Google Scholar 

  3. Howlander N, Noone A, Krapcho M, et al. SEER cancer statistics review, 1975–2012. Bethesda: National Cancer Institute; 2015.

    Google Scholar 

  4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    Article  PubMed  Google Scholar 

  5. Bougie O, Weberpals JI. Clinical considerations of BRCA1- and BRCA2-mutation carriers: a review. Int J Surg Oncol. 2011;2011:374012.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302(5645):643–6.

    Article  CAS  PubMed  Google Scholar 

  7. National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch. Surveillance, Epidemiology, and End Results (SEER) Program. Research Data (1973–2009). Released April 2012 based on November 2011 submission. www.seer.cancer.gov.

  8. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.

    Article  PubMed  Google Scholar 

  9. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.

    Article  PubMed  Google Scholar 

  10. Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM, et al. ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res. 2008;14(17):5594–601.

    Article  CAS  PubMed  Google Scholar 

  11. Deraco M, Baratti D, Laterza B, Balestra MR, Mingrone E, Macri A, et al. Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Eur J Surg Oncol. 2011;37(1):4–9.

    Article  CAS  PubMed  Google Scholar 

  12. Li J, Fadare O, Xiang L, Kong B, Zheng W. Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis. J Hematol Oncol. 2012;5:8. doi:10.1186/1756-8722-5-8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Marquez RT, Baggerly KA, Patterson AP, Liu J, Broaddus R, Frumovitz M, et al. Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon. Clin Cancer Res. 2005;11(17):6116–26.

    Article  CAS  PubMed  Google Scholar 

  14. Bell DA. Origins and molecular pathology of ovarian cancer. Mod Pathol. 2005;18(Suppl 2):S19–32.

    Article  CAS  PubMed  Google Scholar 

  15. Lacey Jr JV, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA. 2002;288(3):334–41.

    Article  CAS  PubMed  Google Scholar 

  16. American Career Society. Cancer facts and figures 2008. 2008.

    Google Scholar 

  17. Merritt MA, Cramer DW. Molecular pathogenesis of endometrial and ovarian cancer. Cancer Biomark. 2010;9(1–6):287–305.

    PubMed  Google Scholar 

  18. Parazzini F, Franceschi S, La Vecchia C, Fasoli M. The epidemiology of ovarian cancer. Gynecol Oncol. 1991;43(1):9–23.

    Article  CAS  PubMed  Google Scholar 

  19. Parazzini F, La Vecchia C, Bocciolone L, Franceschi S. The epidemiology of endometrial cancer. Gynecol Oncol. 1991;41(1):1–16.

    Article  CAS  PubMed  Google Scholar 

  20. Prentice RL, Thomson CA, Caan B, Hubbell FA, Anderson GL, Beresford SA, et al. Low-fat dietary pattern and cancer incidence in the Women’s Health Initiative Dietary Modification Randomized Controlled Trial. J Natl Cancer Inst. 2007;99(20):1534–43.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Punt S, Thijssen VL, Vrolijk J, de Kroon CD, Gorter A, Jordanova ES. Galectin-1, -3 and -9 expression and clinical significance in squamous cervical cancer. PLoS One. 2015;10(6):e0129119.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M. Cancer incidence in five continents. IX ed. IARC Scientific Publications No. 160. Lyon: International Agency for Research on Cancer; 2007.

    Google Scholar 

  23. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9.

    Article  CAS  PubMed  Google Scholar 

  24. Bansal N, Herzog TJ, Shaw RE, Burke WM, Deutsch I, Wright JD. Primary therapy for early-stage cervical cancer: radical hysterectomy vs radiation. Am J Obstet Gynecol. 2009;201(5):485.e1–9.

    Article  Google Scholar 

  25. SEER data for 2000–2004. http://seer.cancer.gov/. Accessed 25 April 2011.

  26. Ries LAG, Harkins D, Krapcho M, et al. SEER cancer statistics review, 1975 to 2003. Bethesda: National Cancer Institute; 2006.

    Google Scholar 

  27. Di Saia PJ, Creasman WT, Mannel RS, McMeekin DS, Mutch DG. Invasive cervical cancer. In: Di Saia PJ, Creasman WT, editors. Clinical gynecologic oncology. 8th ed. Philadelphia: Elsevier; 2012. p. 51–119.

    Google Scholar 

  28. Estape R, Angioli R. Surgical management of advanced and recurrent cervical cancer. Semin Surg Oncol. 1999;16(3):236–41.

    Article  CAS  PubMed  Google Scholar 

  29. Jobsen JJ, Leer JW, Cleton FJ, Hermans J. Treatment of locoregional recurrence of carcinoma of the cervix by radiotherapy after primary surgery. Gynecol Oncol. 1989;33(3):368–71.

    Article  CAS  PubMed  Google Scholar 

  30. Davis NM, Sokolosky M, Stadelman K, Abrams SL, Libra M, Candido S, et al. Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention. Oncotarget. 2014;5(13):4603–50.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008;27(41):5497–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Weigelt B, Warne PH, Downward J. PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene. 2011;30(29):3222–33.

    Article  CAS  PubMed  Google Scholar 

  33. Wheler JJ, Moulder SL, Naing A, Janku F, Piha-Paul SA, Falchook GS, et al. Anastrozole and everolimus in advanced gynecologic and breast malignancies: activity and molecular alterations in the PI3K/AKT/mTOR pathway. Oncotarget. 2014;5(10):3029–38.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Stambolic V. Cancer: precise control of localized signals. Nature. 2015;522(7554):38–40.

    Article  CAS  PubMed  Google Scholar 

  35. Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 1997;57(18):3935–40.

    CAS  PubMed  Google Scholar 

  36. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92(11):924–30.

    Article  CAS  PubMed  Google Scholar 

  37. Dinkelspiel HE, Wright JD, Lewin SN, Herzog TJ. Contemporary clinical management of endometrial cancer. Obstet Gynecol Int. 2013;2013:583891.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell. 2000;100(4):387–90.

    Article  CAS  PubMed  Google Scholar 

  39. Hsu CP, Kao TY, Chang WL, Nieh S, Wang HL, Chung YC. Clinical significance of tumor suppressor PTEN in colorectal carcinoma. Eur J Surg Oncol. 2011;37(2):140–7.

    Article  CAS  PubMed  Google Scholar 

  40. Pan J, Cheng L, Bi X, Zhang X, Liu S, Bai X, et al. Elevation of omega-3 polyunsaturated fatty acids attenuates PTEN-deficiency induced endometrial cancer development through regulation of COX-2 and PGE2 production. Sci Rep. 2015;5:14958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 2006;6(3):184–92.

    Article  CAS  PubMed  Google Scholar 

  42. Adams JR, Schachter NF, Liu JC, Zacksenhaus E, Egan SE. Elevated PI3K signaling drives multiple breast cancer subtypes. Oncotarget. 2011;2(6):435–47.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Liu JC, Wang DY, Egan SE, Zacksenhaus E. Common and distinct features of mammary tumors driven by Pten-deletion or activating Pik3ca mutation. Oncotarget. 2016;7:9060–8.

    PubMed  PubMed Central  Google Scholar 

  44. Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, et al. A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science. 2013;341(6144):399–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bassi C, Ho J, Srikumar T, Dowling RJ, Gorrini C, Miller SJ, et al. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science. 2013;341(6144):395–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Song MS, Carracedo A, Salmena L, Song SJ, Egia A, Malumbres M, et al. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell. 2011;144(2):187–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13(5):283–96.

    CAS  PubMed  Google Scholar 

  48. Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, et al. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med. 2011;17(4):461–9.

    Article  PubMed  CAS  Google Scholar 

  49. Shi Y, Wang J, Chandarlapaty S, Cross J, Thompson C, Rosen N, et al. PTEN is a protein tyrosine phosphatase for IRS1. Nat Struct Mol Biol. 2014;21(6):522–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang S, Liu JC, Kim D, Datti A, Zacksenhaus E. Targeted Pten deletion plus p53-R270H mutation in mouse mammary epithelium induces aggressive claudin-low and basal-like breast cancer. Breast Cancer Res. 2016;18(1):9. doi:10.1186/s13058-015-0668-y.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Guo L, Wu H, Zhu J, Zhang C, Ma J, Lan J, et al. Genetic variations in the PI3K/AKT pathway predict platinum-based neoadjuvant chemotherapeutic sensitivity in squamous cervical cancer. Life Sci. 2015;143:217–24.

    Article  CAS  PubMed  Google Scholar 

  52. Du J, Wang L, Li C, Yang H, Li Y, Hu H, et al. MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway. Tumour Biol. 2016;37:3939–47.

    Article  CAS  PubMed  Google Scholar 

  53. Yang YK, Xi WY, Xi RX, Li JY, Li Q, Gao YE. MicroRNA-494 promotes cervical cancer proliferation through the regulation of PTEN. Oncol Rep. 2015 May;33(5):2393–401.

    CAS  PubMed  Google Scholar 

  54. Moreno-Bueno G, Gamallo C, Perez-Gallego L, de Mora JC, Suarez A, Palacios J. beta-Catenin expression pattern, beta-catenin gene mutations, and microsatellite instability in endometrioid ovarian carcinomas and synchronous endometrial carcinomas. Diagn Mol Pathol. 2001;10(2):116–22.

    Article  CAS  PubMed  Google Scholar 

  55. Wu R, Zhai Y, Fearon ER, Cho KR. Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res. 2001;61(22):8247–55.

    CAS  PubMed  Google Scholar 

  56. Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, et al. Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res. 1998;58(10):2095–7.

    CAS  PubMed  Google Scholar 

  57. Shih I, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164(5):1511–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, et al. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res. 2000;60(24):7052–6.

    CAS  PubMed  Google Scholar 

  59. Hashiguchi Y, Tsuda H, Inoue T, Berkowitz RS, Mok SC. PTEN expression in clear cell adenocarcinoma of the ovary. Gynecol Oncol. 2006;101(1):71–5.

    Article  CAS  PubMed  Google Scholar 

  60. Folgueira MA, Maistro S, Katayama ML, Roela RA, Mundim FG, Nanogaki S, et al. Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series. Biosci Rep. 2013;33(6) doi:10.1042/BSR20130060.

  61. Zhang B, Cao X, Liu Y, Cao W, Zhang F, Zhang S, et al. Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer. BMC Cancer. 2008;8:83. doi:10.1186/1471-2407-8-83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Jung EJ, Moon HG, Cho BI, Jeong CY, Joo YT, Lee YJ, et al. Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer. Int J Cancer. 2007;120(11):2331–8.

    Article  CAS  PubMed  Google Scholar 

  63. Yeung TL, Leung CS, Li F, Wong SS, Mok SC. Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment. Biomolecules. 2016;6(1) doi:10.3390/biom6010003.

  64. Lawrenson K, Grun B, Lee N, Mhawech-Fauceglia P, Kan J, Swenson S, et al. NPPB is a novel candidate biomarker expressed by cancer-associated fibroblasts in epithelial ovarian cancer. Int J Cancer. 2015;136(6):1390–401.

    Article  CAS  PubMed  Google Scholar 

  65. Yeung TL, Leung CS, Mok SC. CAF reprogramming inhibits ovarian cancer progression. Cell Cycle. 2014;13(24):3783–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Yeung TL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, et al. TGF-beta modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 2013;73(16):5016–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Serini G, Gabbiani G. Mechanisms of myofibroblast activity and phenotypic modulation. Exp Cell Res. 1999;250(2):273–83.

    Article  CAS  PubMed  Google Scholar 

  68. Erez N, Glanz S, Raz Y, Avivi C, Barshack I. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. Biochem Biophys Res Commun. 2013;437(3):397–402.

    Article  CAS  PubMed  Google Scholar 

  69. Mueller MM, Fusenig NE. Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer. 2004;4(11):839–49.

    Article  CAS  PubMed  Google Scholar 

  70. Chen H, Yang WW, Wen QT, Xu L, Chen M. TGF-beta induces fibroblast activation protein expression; fibroblast activation protein expression increases the proliferation, adhesion, and migration of HO-8910PM [corrected]. Exp Mol Pathol. 2009;87(3):189–94.

    Article  CAS  PubMed  Google Scholar 

  71. Yang W, Han W, Ye S, Liu D, Wu J, Liu H, et al. Fibroblast activation protein-alpha promotes ovarian cancer cell proliferation and invasion via extracellular and intracellular signaling mechanisms. Exp Mol Pathol. 2013;95(1):105–10.

    Article  CAS  PubMed  Google Scholar 

  72. Ohira S, Itatsu K, Sasaki M, Harada K, Sato Y, Zen Y, et al. Local balance of transforming growth factor-beta1 secreted from cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma. Pathol Int. 2006;56(7):381–9.

    Article  CAS  PubMed  Google Scholar 

  73. Ohira S, Sasaki M, Harada K, Sato Y, Zen Y, Isse K, et al. Possible regulation of migration of intrahepatic cholangiocarcinoma cells by interaction of CXCR4 expressed in carcinoma cells with tumor necrosis factor-alpha and stromal-derived factor-1 released in stroma. Am J Pathol. 2006;168(4):1155–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chang SC, Lin PC, Yang SH, Wang HS, Li AF, Lin JK. SDF-1alpha G801A polymorphism predicts lymph node metastasis in stage T3 colorectal cancer. Ann Surg Oncol. 2009;16(8):2323–30.

    Article  PubMed  Google Scholar 

  75. Daly AJ, McIlreavey L, Irwin CR. Regulation of HGF and SDF-1 expression by oral fibroblasts—implications for invasion of oral cancer. Oral Oncol. 2008;44(7):646–51.

    Article  CAS  PubMed  Google Scholar 

  76. Matsuo Y, Ochi N, Sawai H, Yasuda A, Takahashi H, Funahashi H, et al. CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer. Int J Cancer. 2009;124(4):853–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lau TS, Chung TK, Cheung TH, Chan LK, Cheung LW, Yim SF, et al. Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. J Pathol. 2014;232(1):43–56.

    Article  CAS  PubMed  Google Scholar 

  78. McAndrews KM, Yi J, McGrail DJ, Dawson MR. Enhanced adhesion of stromal cells to invasive cancer cells regulated by cadherin 11. ACS Chem Biol. 2015;10(8):1932–8.

    Article  CAS  PubMed  Google Scholar 

  79. Moran-Jones K, Gloss BS, Murali R, Chang DK, Colvin EK, Jones MD, et al. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer. Oncotarget. 2015;6:44551–62.

    PubMed  PubMed Central  Google Scholar 

  80. Huang R, Wu D, Yuan Y, Li X, Holm R, Trope CG, et al. CD117 expression in fibroblasts-like stromal cells indicates unfavorable clinical outcomes in ovarian carcinoma patients. PLoS One. 2014;9(11):e112209.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Chen L, Yao Y, Sun L, Zhou J, Liu J, Wang J, et al. Clinical implication of the serum galectin-1 expression in epithelial ovarian cancer patients. J Ovarian Res. 2015;8(1):78. doi:10.1186/s13048-015-0206-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T, et al. Galectins: a family of animal beta-galactoside-binding lectins. Cell. 1994;76(4):597–8.

    Article  CAS  PubMed  Google Scholar 

  83. Barondes SH, Cooper DN, Gitt MA, Leffler H. Galectins. Structure and function of a large family of animal lectins. J Biol Chem. 1994;269(33):20807–10.

    CAS  PubMed  Google Scholar 

  84. Camby I, Le Mercier M, Lefranc F, Kiss R. Galectin-1: a small protein with major functions. Glycobiology. 2006;16(11):137R–57R.

    Article  CAS  PubMed  Google Scholar 

  85. Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer. 2005;5(1):29–41.

    Article  CAS  PubMed  Google Scholar 

  86. Wu MH, Hong TM, Cheng HW, Pan SH, Liang YR, Hong HC, et al. Galectin-1-mediated tumor invasion and metastasis, up-regulated matrix metalloproteinase expression, and reorganized actin cytoskeletons. Mol Cancer Res. 2009;7(3):311–8.

    Article  CAS  PubMed  Google Scholar 

  87. Thijssen VL, Poirier F, Baum LG, Griffioen AW. Galectins in the tumor endothelium: opportunities for combined cancer therapy. Blood. 2007;110(8):2819–27.

    Article  CAS  PubMed  Google Scholar 

  88. Thijssen VL, Postel R, Brandwijk RJ, Dings RP, Nesmelova I, Satijn S, et al. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci U S A. 2006;103(43):15975–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Rabinovich GA, Ilarregui JM. Conveying glycan information into T-cell homeostatic programs: a challenging role for galectin-1 in inflammatory and tumor microenvironments. Immunol Rev. 2009;230(1):144–59.

    Article  CAS  PubMed  Google Scholar 

  90. Kovacs-Solyom F, Blasko A, Fajka-Boja R, Katona RL, Vegh L, Novak J, et al. Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1. Immunol Lett. 2010;127(2):108–18.

    Article  CAS  PubMed  Google Scholar 

  91. Xu XC, el-Naggar AK, Lotan R. Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol. 1995;147(3):815–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Chiariotti L, Berlingieri MT, Battaglia C, Benvenuto G, Martelli ML, Salvatore P, et al. Expression of galectin-1 in normal human thyroid gland and in differentiated and poorly differentiated thyroid tumors. Int J Cancer. 1995;64(3):171–5.

    Article  CAS  PubMed  Google Scholar 

  93. Wu MH, Hong HC, Hong TM, Chiang WF, Jin YT, Chen YL. Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression. Clin Cancer Res. 2011;17(6):1306–16.

    Article  CAS  PubMed  Google Scholar 

  94. van den Brule F, Califice S, Garnier F, Fernandez PL, Berchuck A, Castronovo V. Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin. Lab Invest. 2003;83(3):377–86.

    Article  PubMed  CAS  Google Scholar 

  95. Kim HJ, Jeon HK, Cho YJ, Park YA, Choi JJ, Do IG, et al. High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion. Eur J Cancer. 2012;48(12):1914–21.

    Article  CAS  PubMed  Google Scholar 

  96. Zhang P, Zhang P, Shi B, Zhou M, Jiang H, Zhang H, et al. Galectin-1 overexpression promotes progression and chemoresistance to cisplatin in epithelial ovarian cancer. Cell Death Dis. 2014;5:e991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Huang EY, Chanchien CC, Lin H, Wang CC, Wang CJ, Huang CC. Galectin-1 is an independent prognostic factor for local recurrence and survival after definitive radiation therapy for patients with squamous cell carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys. 2013;87(5):975–82.

    Article  CAS  PubMed  Google Scholar 

  98. Benes P, Vetvicka V, Fusek M. Cathepsin D—many functions of one aspartic protease. Crit Rev Oncol Hematol. 2008;68(1):12–28.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Pranjol MZ, Gutowski N, Hannemann M, Whatmore J. The potential role of the proteases cathepsin D and cathepsin L in the progression and metastasis of epithelial ovarian cancer. Biomolecules. 2015;5(4):3260–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Mathieu M, Vignon F, Capony F, Rochefort H. Estradiol down-regulates the mannose-6-phosphate/insulin-like growth factor-II receptor gene and induces cathepsin-D in breast cancer cells: a receptor saturation mechanism to increase the secretion of lysosomal proenzymes. Mol Endocrinol. 1991;5(6):815–22.

    Article  CAS  PubMed  Google Scholar 

  101. Kagedal K, Johansson U, Ollinger K. The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress. FASEB J. 2001;15(9):1592–4.

    CAS  PubMed  Google Scholar 

  102. Heinrich M, Neumeyer J, Jakob M, Hallas C, Tchikov V, Winoto-Morbach S, et al. Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation. Cell Death Differ. 2004;11(5):550–63.

    Article  CAS  PubMed  Google Scholar 

  103. Blomgran R, Zheng L, Stendahl O. Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization. J Leukoc Biol. 2007;81(5):1213–23.

    Article  CAS  PubMed  Google Scholar 

  104. Zuzarte-Luis V, Montero JA, Kawakami Y, Izpisua-Belmonte JC, Hurle JM. Lysosomal cathepsins in embryonic programmed cell death. Dev Biol. 2007;301(1):205–17.

    Article  CAS  PubMed  Google Scholar 

  105. Zuzarte-Luis V, Montero JA, Torre-Perez N, Garcia-Porrero JA, Hurle JM. Cathepsin D gene expression outlines the areas of physiological cell death during embryonic development. Dev Dyn. 2007;236(3):880–5.

    Article  CAS  PubMed  Google Scholar 

  106. Ohri SS, Vashishta A, Proctor M, Fusek M, Vetvicka V. The propeptide of cathepsin D increases proliferation, invasion and metastasis of breast cancer cells. Int J Oncol. 2008;32(2):491–8.

    CAS  PubMed  Google Scholar 

  107. Winiarski BK, Wolanska KI, Rai S, Ahmed T, Acheson N, Gutowski NJ, et al. Epithelial ovarian cancer-induced angiogenic phenotype of human omental microvascular endothelial cells may occur independently of VEGF signaling. Transl Oncol. 2013;6(6):703–14.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Rochefort H. Cathepsin D in breast cancer: a tissue marker associated with metastasis. Eur J Cancer. 1992;28A(11):1780–3.

    Article  CAS  PubMed  Google Scholar 

  109. Rochefort H, Garcia M, Glondu M, Laurent V, Liaudet E, Rey JM, et al. Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview. Clin Chim Acta. 2000;291(2):157–70.

    Article  CAS  PubMed  Google Scholar 

  110. Ferrandina G, Scambia G, Bardelli F, Benedetti Panici P, Mancuso S, Messori A. Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis. Br J Cancer. 1997;76(5):661–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Foekens JA, Look MP, Bolt-de Vries J, Meijer-van Gelder ME, van Putten WL, Klijn JG. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients. Br J Cancer. 1999;79(2):300–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Briozzo P, Badet J, Capony F, Pieri I, Montcourrier P, Barritault D, et al. MCF7 mammary cancer cells respond to bFGF and internalize it following its release from extracellular matrix: a permissive role of cathepsin D. Exp Cell Res. 1991;194(2):252–9.

    Article  CAS  PubMed  Google Scholar 

  113. Losch A, Kohlberger P, Gitsch G, Kaider A, Breitenecker G, Kainz C. Lysosomal protease cathepsin D is a prognostic marker in endometrial cancer. Br J Cancer. 1996;73(12):1525–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Nazeer T, Malfetano JH, Rosano TG, Ross JS. Correlation of tumor cytosol cathepsin D with differentiation and invasiveness of endometrial adenocarcinoma. Am J Clin Pathol. 1992;97(6):764–9.

    Article  CAS  PubMed  Google Scholar 

  115. Henzen-Logmans SC, Fieret EJ, Berns EM, van der Burg ME, Klijn JG, Foekens JA. Ki-67 staining in benign, borderline, malignant primary and metastatic ovarian tumors: correlation with steroid receptors, epidermal-growth-factor receptor and cathepsin D. Int J Cancer. 1994;57(4):468–72.

    Article  CAS  PubMed  Google Scholar 

  116. Losch A, Schindl M, Kohlberger P, Lahodny J, Breitenecker G, Horvat R, et al. Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density. Gynecol Oncol. 2004;92(2):545–52.

    Article  CAS  PubMed  Google Scholar 

  117. Chai Y, Wu W, Zhou C, Zhou J. The potential prognostic value of cathepsin D protein in serous ovarian cancer. Arch Gynecol Obstet. 2012;286(2):465–71.

    Article  CAS  PubMed  Google Scholar 

  118. Winiarski BK, Cope N, Alexander M, Pilling LC, Warren S, Acheson N, et al. Clinical relevance of increased endothelial and mesothelial expression of proangiogenic proteases and VEGFA in the omentum of patients with metastatic ovarian high-grade serous carcinoma. Transl Oncol. 2014;7(2):267–276.e4.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Rochefort H, Capony F, Garcia M, Cavailles V, Freiss G, Chambon M, et al. Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? J Cell Biochem. 1987;35(1):17–29.

    Article  CAS  PubMed  Google Scholar 

  120. Vignon F, Capony F, Chambon M, Freiss G, Garcia M, Rochefort H. Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52K protein. Endocrinology. 1986;118(4):1537–45.

    Article  CAS  PubMed  Google Scholar 

  121. Kirschke H, Langner J, Wiederanders B, Ansorge S, Bohley P. Cathepsin L. A new proteinase from rat-liver lysosomes. Eur J Biochem. 1977;74(2):293–301.

    Article  CAS  PubMed  Google Scholar 

  122. Kominami E, Ueno T, Muno D, Katunuma N. The selective role of cathepsins B and D in the lysosomal degradation of endogenous and exogenous proteins. FEBS Lett. 1991;287(1–2):189–92.

    Article  CAS  PubMed  Google Scholar 

  123. Nguyen Q, Mort JS, Roughley PJ. Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B. Biochem J. 1990;266(2):569–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Nosaka AY, Kanaori K, Teno N, Togame H, Inaoka T, Takai M, et al. Conformational studies on the specific cleavage site of Type I collagen (alpha-1) fragment (157-192) by cathepsins K and L by proton NMR spectroscopy. Bioorg Med Chem. 1999;7(2):375–9.

    Article  CAS  PubMed  Google Scholar 

  125. Mason RW, Johnson DA, Barrett AJ, Chapman HA. Elastinolytic activity of human cathepsin L. Biochem J. 1986;233(3):925–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Ishidoh K, Kominami E. Procathepsin L degrades extracellular matrix proteins in the presence of glycosaminoglycans in vitro. Biochem Biophys Res Commun. 1995;217(2):624–31.

    Article  CAS  PubMed  Google Scholar 

  127. Maciewicz RA, Wotton SF, Etherington DJ, Duance VC. Susceptibility of the cartilage collagens types II, IX and XI to degradation by the cysteine proteinases, cathepsins B and L. FEBS Lett. 1990;269(1):189–93.

    Article  CAS  PubMed  Google Scholar 

  128. Maciewicz RA, Wotton SF. Degradation of cartilage matrix components by the cysteine proteinases, cathepsins B and L. Biomed Biochim Acta. 1991;50(4–6):561–4.

    CAS  PubMed  Google Scholar 

  129. Nishida Y, Kohno K, Kawamata T, Morimitsu K, Kuwano M, Miyakawa I. Increased cathepsin L levels in serum in some patients with ovarian cancer: comparison with CA125 and CA72-4. Gynecol Oncol. 1995;56(3):357–61.

    Article  CAS  PubMed  Google Scholar 

  130. Zhang W, Wang S, Wang Q, Yang Z, Pan Z, Li L. Overexpression of cysteine cathepsin L is a marker of invasion and metastasis in ovarian cancer. Oncol Rep. 2014;31(3):1334–42.

    CAS  PubMed  Google Scholar 

  131. Zhang L, Wei L, Shen G, He B, Gong W, Min N, et al. Cathepsin L is involved in proliferation and invasion of ovarian cancer cells. Mol Med Rep. 2015;11(1):468–74.

    CAS  PubMed  Google Scholar 

  132. Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30(Suppl 5):F88–99.

    Article  PubMed  Google Scholar 

  133. Carozzi F, Visioli CB, Confortini M, Iossa A, Mantellini P, Burroni E, et al. hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy. Br J Cancer. 2013;109(7):1766–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Meijer CJ, Berkhof H, Heideman DA, Hesselink AT, Snijders PJ. Validation of high-risk HPV tests for primary cervical screening. J Clin Virol. 2009;46(Suppl 3):S1–4.

    Article  PubMed  Google Scholar 

  135. Tornesello ML, Buonaguro L, Giorgi-Rossi P, Buonaguro FM. Viral and cellular biomarkers in the diagnosis of cervical intraepithelial neoplasia and cancer. Biomed Res Int. 2013;2013:519619.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol. 2010;11(3):249–57.

    Article  CAS  PubMed  Google Scholar 

  137. Castle PE, Fetterman B, Poitras N, Lorey T, Shaber R, Kinney W. Relationship of atypical glandular cell cytology, age, and human papillomavirus detection to cervical and endometrial cancer risks. Obstet Gynecol. 2010;115(2 Pt 1):243–8.

    Article  PubMed  Google Scholar 

  138. Khleif SN, DeGregori J, Yee CL, Otterson GA, Kaye FJ, Nevins JR, et al. Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci U S A. 1996;93(9):4350–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Nakao Y, Yang X, Yokoyama M, Ferenczy A, Tang SC, Pater MM, et al. Induction of p16 during immortalization by HPV 16 and 18 and not during malignant transformation. Br J Cancer. 1997;75(10):1410–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Pannone G, Rodolico V, Santoro A, Lo Muzio L, Franco R, Botti G, et al. Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 immunohistochemistry, consensus PCR HPV-DNA, and in situ hybridization. Infect Agent Cancer. 2012;7:4. doi:10.1186/1750-9378-7-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Zhang Q, Kuhn L, Denny LA, De Souza M, Taylor S, Wright Jr TC. Impact of utilizing p16INK4A immunohistochemistry on estimated performance of three cervical cancer screening tests. Int J Cancer. 2007;120(2):351–6.

    Article  CAS  PubMed  Google Scholar 

  142. Roelens J, Reuschenbach M, von Knebel Doeberitz M, Wentzensen N, Bergeron C, Arbyn M. p16INK4a immunocytochemistry versus human papillomavirus testing for triage of women with minor cytologic abnormalities: a systematic review and meta-analysis. Cancer Cytopathol. 2012;120(5):294–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Reuschenbach M, Seiz M, von Knebel DC, Vinokurova S, Duwe A, Ridder R, et al. Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki-67 in epithelial cells. Int J Cancer. 2012;130(2):388–94.

    Article  CAS  PubMed  Google Scholar 

  144. Schmidt D, Bergeron C, Denton KJ, Ridder R, European CINtec Cytology Study Group. p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal papanicolaou cytology study. Cancer Cytopathol. 2011;119(3):158–66.

    Article  PubMed  Google Scholar 

  145. Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011;6(9):1083–98.

    Article  PubMed  Google Scholar 

  146. Depuydt CE, Makar AP, Ruymbeke MJ, Benoy IH, Vereecken AJ, Bogers JJ. BD-ProExC as adjunct molecular marker for improved detection of CIN2+ after HPV primary screening. Cancer Epidemiol Biomarkers Prev. 2011;20(4):628–37.

    Article  CAS  PubMed  Google Scholar 

  147. Van Doorslaer K, Burk RD. Association between hTERT activation by HPV E6 proteins and oncogenic risk. Virology. 2012;433(1):216–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Liu H, Liu S, Wang H, Xie X, Chen X, Zhang X, et al. Genomic amplification of the human telomerase gene (hTERC) associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer. Diagn Pathol. 2012;7:147. doi:10.1186/1746-1596-7-147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Fiorucci G, Chiantore MV, Mangino G, Percario ZA, Affabris E, Romeo G. Cancer regulator microRNA: potential relevance in diagnosis, prognosis and treatment of cancer. Curr Med Chem. 2012;19(4):461–74.

    Article  CAS  PubMed  Google Scholar 

  150. Gadducci A, Guerrieri ME, Greco C. Tissue biomarkers as prognostic variables of cervical cancer. Crit Rev Oncol Hematol. 2013;86(2):104–29.

    Article  PubMed  Google Scholar 

  151. Xu J, Li Y, Wang F, Wang X, Cheng B, Ye F, et al. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene. 2013;32(8):976–87.

    Article  CAS  PubMed  Google Scholar 

  152. Li Y, Liu J, Yuan C, Cui B, Zou X, Qiao Y. High-risk human papillomavirus reduces the expression of microRNA-218 in women with cervical intraepithelial neoplasia. J Int Med Res. 2010;38(5):1730–6.

    Article  CAS  PubMed  Google Scholar 

  153. Wang F, Li Y, Zhou J, Xu J, Peng C, Ye F, et al. miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol. 2011;179(5):2580–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21.

    Article  CAS  PubMed  Google Scholar 

  155. Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31(1):27–36.

    Article  CAS  PubMed  Google Scholar 

  156. Cuzick J, Bergeron C, von Knebel DM, Gravitt P, Jeronimo J, Lorincz AT, et al. New technologies and procedures for cervical cancer screening. Vaccine. 2012;30(Suppl 5):F107–16.

    Article  CAS  PubMed  Google Scholar 

  157. Wentzensen N, Sun C, Ghosh A, Kinney W, Mirabello L, Wacholder S, et al. Methylation of HPV18, HPV31, and HPV45 genomes and cervical intraepithelial neoplasia grade 3. J Natl Cancer Inst. 2012;104(22):1738–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Mirabello L, Sun C, Ghosh A, Rodriguez AC, Schiffman M, Wentzensen N, et al. Methylation of human papillomavirus type 16 genome and risk of cervical precancer in a Costa Rican population. J Natl Cancer Inst. 2012;104(7):556–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Sova P, Feng Q, Geiss G, Wood T, Strauss R, Rudolf V, et al. Discovery of novel methylation biomarkers in cervical carcinoma by global demethylation and microarray analysis. Cancer Epidemiol Biomarkers Prev. 2006;15(1):114–23.

    Article  CAS  PubMed  Google Scholar 

  160. Wang SS, Smiraglia DJ, Wu YZ, Ghosh S, Rader JS, Cho KR, et al. Identification of novel methylation markers in cervical cancer using restriction landmark genomic scanning. Cancer Res. 2008;68(7):2489–97.

    Article  CAS  PubMed  Google Scholar 

  161. Steenbergen RD, Kramer D, Braakhuis BJ, Stern PL, Verheijen RH, Meijer CJ, et al. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst. 2004;96(4):294–305.

    Article  CAS  PubMed  Google Scholar 

  162. Wentzensen N, Sherman ME, Schiffman M, Wang SS. Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Gynecol Oncol. 2009;112(2):293–9.

    Article  CAS  PubMed  Google Scholar 

  163. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.

    Article  CAS  PubMed  Google Scholar 

  164. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–31.

    Article  CAS  PubMed  Google Scholar 

  165. Ambros V. microRNAs: tiny regulators with great potential. Cell. 2001;107(7):823–6.

    Article  CAS  PubMed  Google Scholar 

  166. Forman JJ, Legesse-Miller A, Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A. 2008;105(39):14879–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci U S A. 2007;104(23):9667–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101(9):2999–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Melo SA, Moutinho C, Ropero S, Calin GA, Rossi S, Spizzo R, et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell. 2010;18(4):303–15.

    Article  CAS  PubMed  Google Scholar 

  171. Helland A, Anglesio MS, George J, Cowin PA, Johnstone CN, House CM, et al. Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. PLoS One. 2011;6(4):e18064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Schrauder MG, Strick R, Schulz-Wendtland R, Strissel PL, Kahmann L, Loehberg CR, et al. Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection. PLoS One. 2012;7(1):e29770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. O’Day E, Lal A. MicroRNAs and their target gene networks in breast cancer. Breast Cancer Res. 2010;12(2):201.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.

    Article  CAS  PubMed  Google Scholar 

  175. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, et al. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A. 2008;105(35):13021–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 2009;11(3):R27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H. miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res. 2008;68(13):5004–8.

    Article  CAS  PubMed  Google Scholar 

  178. Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol. 2007;8(10):R214.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008;14(11):2348–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Van der Auwera I, Limame R, van Dam P, Vermeulen PB, Dirix LY, Van Laere SJ. Integrated miRNA and mRNA expression profiling of the inflammatory breast cancer subtype. Br J Cancer. 2010;103(4):532–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Cai Y, Yan X, Zhang G, Zhao W, Jiao S. MicroRNA-205 increases the sensitivity of docetaxel in breast cancer. Oncol Lett. 2016;11(2):1105–9.

    PubMed  Google Scholar 

  182. Pal MK, Jaiswar SP, Dwivedi VN, Tripathi AK, Dwivedi A, Sankhwar P. MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer. Cancer Biol Med. 2015;12(4):328–41.

    PubMed  PubMed Central  Google Scholar 

  183. Chen PS, Su JL, Hung MC. Dysregulation of microRNAs in cancer. J Biomed Sci. 2012;19:90. doi:10.1186/1423-0127-19-90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.

    Article  CAS  PubMed  Google Scholar 

  185. Zhang W, Dahlberg JE, Tam W. MicroRNAs in tumorigenesis: a primer. Am J Pathol. 2007;171(3):728–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Parikh A, Lee C, Joseph P, Marchini S, Baccarini A, Kolev V, et al. microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. Nat Commun. 2014;5:2977.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  187. Wang X, Cao L, Wang Y, Wang X, Liu N, You Y. Regulation of let-7 and its target oncogenes (review). Oncol Lett. 2012;3(5):955–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Gregory PA, Bracken CP, Bert AG, Goodall GJ. MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle. 2008;7(20):3112–8.

    Article  CAS  PubMed  Google Scholar 

  189. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601.

    Article  CAS  PubMed  Google Scholar 

  190. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283(22):14910–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Leskela S, Leandro-Garcia LJ, Mendiola M, Barriuso J, Inglada-Perez L, Munoz I, et al. The miR-200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients. Endocr Relat Cancer. 2010;18(1):85–95.

    Article  PubMed  CAS  Google Scholar 

  193. Sun N, Zhang Q, Xu C, Zhao Q, Ma Y, Lu X, et al. Molecular regulation of ovarian cancer cell invasion. Tumour Biol. 2014;35(11):11359–66.

    Article  CAS  PubMed  Google Scholar 

  194. Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol. 2011;195(3):417–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Corney DC, Hwang CI, Matoso A, Vogt M, Flesken-Nikitin A, Godwin AK, et al. Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res. 2010;16(4):1119–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Mateescu B, Batista L, Cardon M, Gruosso T, de Feraudy Y, Mariani O, et al. miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response. Nat Med. 2011;17(12):1627–35.

    Article  CAS  PubMed  Google Scholar 

  197. Yang H, Kong W, He L, Zhao JJ, O’Donnell JD, Wang J, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008;68(2):425–33.

    Article  CAS  PubMed  Google Scholar 

  198. Lou Y, Yang X, Wang F, Cui Z, Huang Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med. 2010;26(6):819–27.

    Article  CAS  PubMed  Google Scholar 

  199. Nagaraja AK, Creighton CJ, Yu Z, Zhu H, Gunaratne PH, Reid JG, et al. A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol. 2010;24(2):447–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Peng DX, Luo M, Qiu LW, He YL, Wang XF. Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer. Oncol Rep. 2012;27(4):1238–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67(18):8699–707.

    Article  CAS  PubMed  Google Scholar 

  202. Wyman SK, Parkin RK, Mitchell PS, Fritz BR, O'Briant K, Godwin AK, et al. Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One. 2009;4(4):e5311.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  203. Lee H, Park CS, Deftereos G, Morihara J, Stern JE, Hawes SE, et al. MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features. World J Surg Oncol. 2012;10:174.

    Article  PubMed  PubMed Central  Google Scholar 

  204. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009;112(1):55–9.

    Article  CAS  PubMed  Google Scholar 

  205. Eitan R, Kushnir M, Lithwick-Yanai G, David MB, Hoshen M, Glezerman M, et al. Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol Oncol. 2009;114(2):253–9.

    Article  CAS  PubMed  Google Scholar 

  206. Xu YZ, Xi QH, Ge WL, Zhang XQ. Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer. Asian Pac J Cancer Prev. 2013;14(2):1057–60.

    Article  PubMed  Google Scholar 

  207. Wan WN, Zhang YQ, Wang XM, Liu YJ, Zhang YX, Que YH, et al. Down-regulated miR-22 as predictive biomarkers for prognosis of epithelial ovarian cancer. Diagn Pathol. 2014;9:178. doi:10.1186/s13000-014-0178-8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  208. Vecchione A, Belletti B, Lovat F, Volinia S, Chiappetta G, Giglio S, et al. A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis. Proc Natl Acad Sci U S A. 2013;110(24):9845–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Pulmonology, Medical University Graz, Auenbruggerplatz 15, 8036, Graz, Austria

    Elisabeth Smolle

Authors
  1. Elisabeth Smolle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elisabeth Smolle .

Editor information

Editors and Affiliations

  1. Department of Pathology, Medical Faculty, Otto von Guericke University Magdeburg, Magdeburg, Germany

    Johannes Haybaeck

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Smolle, E. (2017). Molecular Carcinogenesis in Gynecologic Neoplasias. In: Haybaeck, J. (eds) Mechanisms of Molecular Carcinogenesis – Volume 2. Springer, Cham. https://doi.org/10.1007/978-3-319-53661-3_11

Download citation

Publish with us

Policies and ethics

Search

Navigation