Skip to main content
SpringerLink
Log in

Cadherin-Catenin Signaling in Ovarian Cancer Progression

  • Chapter
  • First Online:
Signal Transduction in Cancer Metastasis

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 15))

  • 1130 Accesses

Abstract

Ovarian cancer is a highly metastatic disease and has the highest mortality rate of all gynecological tumors. In contrast to many other types of cancer that metastasize through lymphatics and/or hematogenous routes, ovarian cancer metastasizes by peritoneal dissemination, which relies on the ability of cancer cells to detach from the primary tumor, adhere to, and eventually invade through the peritoneum. This involves dynamic changes in cell-cell adhesion, which is primarily mediated by cell surface receptors known as cadherins. In this review, we will describe the unique profiles of cadherins with their associated signal molecules, catenins, in ovarian cancer and the roles of these adhesion molecules in disease development, tumor cell progression, and the formation of ascites. We will discuss how cadherins perform these functions and their link to a variety of signaling pathways. Finally, we will review the recent findings regarding the potential of cadherins as new therapeutic targets in the treatment of ovarian cancer.

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. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA. Cancer. J. Clin. 2008; 58(2): 71–96.

    Article  PubMed  Google Scholar 

  2. Goodman MT, Shvetsov YB. Incidence of ovarian, peritoneal, and fallopian tube carcinomas in the United States, 1995–2004. Cancer. Epidemiol. Biomarkers. Prev. 2009; 18(1): 132–139.

    Article  PubMed  Google Scholar 

  3. Ansell SM, Rapoport BL, Falkson G, Raats JI, Moeken CM. Survival determinants in patients with advanced ovarian cancer. Gynecol. Oncol. 1993; 50(2): 215–220.

    Article  PubMed  CAS  Google Scholar 

  4. Cormio G, Rossi C, Cazzolla A, Resta L, Loverro G Greco P, et al. Distant metastases in ovarian carcinoma. Int. J. Gynecol. Cancer. 2003; 13(2): 125–129.

    Article  PubMed  CAS  Google Scholar 

  5. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer. 2002; 2(8): 563–572.

    Google Scholar 

  6. Knudsen KA, Soler AP, Johnson KR, Wheelock MJ. Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin. J. Cell. Biol. 1995; 130(1): 67–77.

    Article  PubMed  CAS  Google Scholar 

  7. Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Miyazawa K, Kitamura N, et al. Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. J. Cell. Biol. 1995; 128(5): 949–957.

    Article  PubMed  CAS  Google Scholar 

  8. Crawford HC, Fingleton BM, Rudolph-Owen LA, Goss KJ, Rubinfeld B, Polakis P, et al. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 1999; 18(18): 2883–2891.

    Article  PubMed  CAS  Google Scholar 

  9. Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’Amico M, Pestell R, et al. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc. Natl. Acad. Sci. USA 1999; 96(10): 5522–5527.

    Article  PubMed  CAS  Google Scholar 

  10. Noren NK, Liu BP, Burridge K, Kreft B. p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J. Cell. Biol. 2000; 150(3): 567–580.

    Article  PubMed  CAS  Google Scholar 

  11. Grosheva I, Shtutman M, Elbaum M, Bershadsky AD. p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion. J. Cell. Sci. 2001; 114(Pt 4): 695–707.

    PubMed  CAS  Google Scholar 

  12. Pece S. Gutkind JS. Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell-cell contact formation. J. Biol. Chem. 2000; 275(52): 41227–41233.

    Article  PubMed  CAS  Google Scholar 

  13. Qian X, Karpova T, Sheppard AM, McNally J, Lowy DR. E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases. Embo. J. 2004; 23(8): 1739–1748.

    Article  PubMed  CAS  Google Scholar 

  14. Suyama K, Shapiro I, Guttman M, Hazan RB. A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer. Cell. 2002; 2(4): 301–314.

    Article  PubMed  CAS  Google Scholar 

  15. Sundfeldt K, Piontkewitz Y, Billig H, Hedin L. E-cadherin-catenin complex in the rat ovary: cell-specific expression during folliculogenesis and luteal formation. J. Reprod. Fertil. 2000; 118(2): 375–385.

    Article  PubMed  CAS  Google Scholar 

  16. Machell NH, Farookhi R. E- and N-cadherin expression and distribution during luteinization in the rat ovary. Reproduction 2003; 125(6): 791–800.

    Article  PubMed  CAS  Google Scholar 

  17. Wong AS, Maines-Bandiera SL, Rosen B, Wheelock MJ, Johnson KR, Leung PC, et al. Constitutive and conditional cadherin expression in cultured human ovarian surface epithelium: influence of family history of ovarian cancer. Int. J. Cancer. 1999; 81(2): 180–188.

    Article  PubMed  CAS  Google Scholar 

  18. Peralta Soler A, Knudsen KA, Tecson-Miguel A, McBrearty FX, Han AC, Salazar H. Expression of E-cadherin and N-cadherin in surface epithelial-stromal tumors of the ovary distinguishes mucinous from serous and endometrioid tumors. Hum. Pathol. 1997; 28(6): 734–739.

    Article  PubMed  CAS  Google Scholar 

  19. Darai E, Scoazec JY, Walker-Combrouze F, Mlika-Cabanne N, Feldmann G, Madelenat P, et al. Expression of cadherins in benign, borderline, and malignant ovarian epithelial tumors: a clinicopathologic study of 60 cases. Hum. Pathol. 1997; 28(8): 922–928.

    Article  PubMed  CAS  Google Scholar 

  20. Sarrio D, Moreno-Bueno G, Sanchez-Estevez C, Banon-Rodriguez I, Hernandez-Cortes G, Hardisson D, et al. Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas. Hum. Pathol. 2006; 37(8): 1042–1049.

    Article  PubMed  CAS  Google Scholar 

  21. Shimazui T, Giroldi LA, Bringuier PP, Oosterwijk E, Schalken JA. Complex cadherin expression in renal cell carcinoma. Cancer. Res. 1996; 56(14): s3234–3237.

    PubMed  CAS  Google Scholar 

  22. Peralta Soler A, Knudsen KA, Jaurand MC, Johnson KR, Wheelock MJ, Klein-Szanto AJ, et al. The differential expression of N-cadherin and E-cadherin distinguishes pleural mesotheliomas from lung adenocarcinomas.Hum. Pathol. 1995; 26(12): 1363–1369.

    Article  PubMed  CAS  Google Scholar 

  23. Hay ED. An overview of epithelio-mesenchymal transformation. Acta. Anat. (Basel) 1995; 154(1): 8–20.

    Article  CAS  Google Scholar 

  24. Sundfeldt K, Piontkewitz Y, Ivarsson K, Nilsson O, Hellberg P, Brannstrom M, et al. E-cadherin expression in human epithelial ovarian cancer and normal ovary. Int. J. Cancer. 1997; 74(3): 275–280.

    Article  PubMed  CAS  Google Scholar 

  25. Auersperg N, Pan J, Grove BD, Peterson T, Fisher J, Maines-Bandiera S, et al. E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. Proc. Natl. Acad. Sci. USA 1999; 96(11): 6249–6254.

    Article  PubMed  CAS  Google Scholar 

  26. Davies BR, Worsley SD, Ponder BA. Expression of E-cadherin, alpha-catenin and beta-catenin in normal ovarian surface epithelium and epithelial ovarian cancers. Histopathology 1998; 32(1): 69–80.

    Article  PubMed  CAS  Google Scholar 

  27. Maines-Bandiera SL, Auersperg N. Increased E-cadherin expression in ovarian surface epithelium: an early step in metaplasia and dysplasia? Int. J. Gynecol. Pathol. 1997; 16(3): 250–255.

    Article  PubMed  CAS  Google Scholar 

  28. Fujioka T, Takebayashi Y, Kihana T, Kusanagi Y, Hamada K, Ochi H, et al. Expression of E-cadherin and beta-catenin in primary and peritoneal metastatic ovarian carcinoma. Oncol. Rep. 2001; 8(2): 249–255.

    PubMed  CAS  Google Scholar 

  29. Faleiro-Rodrigues C, Macedo-Pinto I, Pereira D, Lopes CS. Prognostic value of E-cadherin immunoexpression in patients with primary ovarian carcinomas. Ann. Oncol. 2004; 15(10): 1535–1542.

    Article  PubMed  CAS  Google Scholar 

  30. Faleiro-Rodrigues C, Macedo-Pinto I, Pereira D, Ferreira VM, Lopes CS. Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas. Hum. Pathol. 2004; 35(6): 663–669.

    Article  PubMed  CAS  Google Scholar 

  31. Davidson B, Gotlieb WH, Ben-Baruch G, Nesland JM, Bryne M, Goldberg I, et al. E-Cadherin complex protein expression and survival in ovarian carcinoma. Gynecol. Oncol. 2000; 79(3): 362–371.

    Article  PubMed  CAS  Google Scholar 

  32. Davidson B, Berner A, Nesland JM, Risberg B, Berner HS, Trope CG, et al. E-cadherin and alpha-, beta-, and gamma-catenin protein expression is up-regulated in ovarian carcinoma cells in serous effusions. J. Pathol. 2000; 192(4): 460–469.

    Article  PubMed  CAS  Google Scholar 

  33. Patel IS, Madan P, Getsios S, Bertrand MA, MacCalman CD. Cadherin switching in ovarian cancer progression. Int. J. Cancer. 2003; 106(2): 172–177.

    Article  PubMed  CAS  Google Scholar 

  34. Scully RE. Pathology of ovarian cancer precursors. J. Cell. Biochem. Suppl. 1995; 23: 208–218.

    Article  PubMed  CAS  Google Scholar 

  35. Nose A. Takeichi M. A novel cadherin cell adhesion molecule: its expression patterns associated with implantation and organogenesis of mouse embryos. J. Cell. Biol. 1986; 103(6 Pt 2): 2649–2658.

    Article  PubMed  CAS  Google Scholar 

  36. Shimoyama Y, Hirohashi S, Hirano S, Noguchi M, Shimosato Y, Takeichi M, et al. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer. Res. 1989; 49(8): 2128–2133.

    PubMed  CAS  Google Scholar 

  37. van der Linden PJ, de Goeij AF, Dunselman GA, Erkens HW, Evers JL. Expression of cadherins and integrins in human endometrium throughout the menstrual cycle. Fertil. Steril. 1995; 63(6): 1210–1216.

    PubMed  Google Scholar 

  38. Peralta Soler A, Knudsen KA, Salazar H, Han AC, Keshgegian AA. P-cadherin expression in breast carcinoma indicates poor survival. Cancer 1999; 86(7): 1263–1272.

    Article  PubMed  CAS  Google Scholar 

  39. Hardy RG, Tselepis C, Hoyland J, Wallis Y, Pretlow TP, Talbot I, et al. Aberrant P-cadherin expression is an early event in hyperplastic and dysplastic transformation in the colon. Gut 2002; 50(4): 513–519.

    Article  PubMed  CAS  Google Scholar 

  40. Taniuchi K, Nakagawa H, Hosokawa M, Nakamura T, Eguchi H, Ohigashi H, et al. Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer. Res. 2005; 65(8): 3092–3099.

    PubMed  CAS  Google Scholar 

  41. Stefansson IM, Salvesen HB, Akslen LA. Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer. J. Clin. Oncol. 2004; 22(7): 1242–1252.

    Article  PubMed  CAS  Google Scholar 

  42. Hsu MY, Wheelock MJ, Johnson KR, Herlyn M. Shifts in cadherin profiles between human normal melanocytes and melanomas. J. Investig. Dermatol. Symp. Proc. 1996; 1(2): 188–194.

    PubMed  CAS  Google Scholar 

  43. Lee SW. H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nat. Med. 1996; 2(7): 776–782.

    Article  PubMed  CAS  Google Scholar 

  44. Sato M, Mori Y, Sakurada A, Fujimura S, Horii A. The H-cadherin (CDH13) gene is inactivated in human lung cancer. Hum. Genet. 1998; 103(1): 96–101.

    Article  PubMed  CAS  Google Scholar 

  45. Mori Y, Matsunaga M, Abe T, Fukushige S, Miura K, Sunamura M, et al. Chromosome band 16q24 is frequently deleted in human gastric cancer. Br. J. Cancer. 1999; 80(3–4): 556–562.

    Article  PubMed  CAS  Google Scholar 

  46. Kawakami M, Staub J, Cliby W, Hartmann L, Smith DI, Shridhar V. Involvement of H-cadherin (CDH13) on 16q in the region of frequent deletion in ovarian cancer. Int. J. Oncol. 1999; 15(4): 715–720.

    PubMed  CAS  Google Scholar 

  47. Lee SW, Reimer CL, Campbell DB, Cheresh P, Duda RB, Kocher O. H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo. Carcinogenesis 1998; 19(6): 1157–1159.

    Article  PubMed  CAS  Google Scholar 

  48. Lambeng N, Wallez Y, Rampon C, Cand F, Christe G, Gulino-Debrac D, et al. Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues. Circ. Res. 2005; 96(3): 384–391.

    Article  PubMed  CAS  Google Scholar 

  49. Rabascio C, Muratori E, Mancuso P, Calleri A, Raia V, Foutz T, et al. Assessing tumor angiogenesis: increased circulating VE-cadherin RNA in patients with cancer indicates viability of circulating endothelial cells. Cancer. Res. 2004; 64(12): 4373–4377.

    Article  PubMed  CAS  Google Scholar 

  50. Xiang YY, Tanaka M, Suzuki M, Igarashi H, Kiyokawa E, Naito Y, et al. Isolation of complementary DNA encoding K-cadherin, a novel rat cadherin preferentially expressed in fetal kidney and kidney carcinoma. Cancer. Res. 1994; 54(11): 3034–3041.

    PubMed  CAS  Google Scholar 

  51. Sellar GC, Li L, Watt KP, Nelkin BD, Rabiasz GJ, Stronach EA, et al. BARX2 induces cadherin 6 expression and is a functional suppressor of ovarian cancer progression. Cancer. Res. 2001; 61(19): 6977–6981.

    PubMed  CAS  Google Scholar 

  52. Hibbs K, Skubitz KM, Pambuccian SE, Casey RC, Burleson KM, Oegema TR, Jr., et al. Differential gene expression in ovarian carcinoma: identification of potential biomarkers. Am. J. Pathol. 2004; 165(2): 397–414.

    Article  PubMed  CAS  Google Scholar 

  53. Kobel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS. Med. 2008; 5(12): e232.

    Article  PubMed  CAS  Google Scholar 

  54. Simonneau L, Kitagawa M, Suzuki S, Thiery JP. Cadherin 11 expression marks the mesenchymal phenotype: towards new functions for cadherins? Cell. Adhes. Commun. 1995; 3(2): 115–130.

    Article  PubMed  CAS  Google Scholar 

  55. Imai T, Horiuchi A, Shiozawa T, Osada R, Kikuchi N, Ohira S, et al. Elevated expression of E-cadherin and alpha-, beta-, and gamma-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas. Hum. Pathol. 2004; 35(12): 1469–1476.

    Article  PubMed  CAS  Google Scholar 

  56. Anttila M, Kosma VM, Ji H, Wei-Ling X, Puolakka J, Juhola M, et al. Clinical significance of alpha-catenin, collagen IV, and Ki-67 expression in epithelial ovarian cancer. J. Clin. Oncol. 1998; 16(8): 2591–2600.

    PubMed  CAS  Google Scholar 

  57. Tuhkanen H, Anttila M, Kosma VM, Puolakka J, Juhola M, Heinonen S, et al. Marked allelic imbalance on chromosome 5q31 does not explain alpha-catenin expression in epithelial ovarian cancer. Gynecol. Oncol. 2004; 94(2): 416–421.

    Article  PubMed  CAS  Google Scholar 

  58. Rask K, Nilsson A, Brannstrom M, Carlsson P, Hellberg P, Janson PO, et al. Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3beta. Br. J. Cancer. 2003; 89(7): 1298–1304.

    Article  PubMed  CAS  Google Scholar 

  59. Gamallo C, Palacios J, Moreno G, Calvo de Mora J, Suarez A, Armas A. beta-catenin expression pattern in stage I and II ovarian carcinomas : relationship with beta-catenin gene mutations, clinicopathological features, and clinical outcome. Am J. Pathol. 1999; 155(2): 527–536.

    CAS  Google Scholar 

  60. Voutilainen KA, Anttila MA, Sillanpaa SM, Ropponen KM, Saarikoski SV, Juhola MT, et al. Prognostic significance of E-cadherin-catenin complex in epithelial ovarian cancer. J. Clin. Pathol. 2006; 59(5): 460–467.

    Article  PubMed  CAS  Google Scholar 

  61. Faleiro-Rodrigues C, Macedo-Pinto I, Pereira D, Lopes CS. Loss of beta-catenin is associated with poor survival in ovarian carcinomas. Int. J. Gynecol. Pathol. 2004; 23(4): 337–346.

    Article  PubMed  Google Scholar 

  62. Palacios J. Gamallo C. Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas. Cancer. Res. 1998; 58(7): 1344–1347.

    PubMed  CAS  Google Scholar 

  63. Furlong MT Morin PJ. Rare activation of the TCF/beta-catenin pathway in ovarian cancer. Gynecol. Oncol. 2000; 77(1): 97–104.

    Article  PubMed  CAS  Google Scholar 

  64. Wright K, Wilson P, Morland S, Campbell I, Walsh M, Hurst T, et al. beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours. Int. J. Cancer. 1999; 82(5): 625–629.

    Article  PubMed  CAS  Google Scholar 

  65. Kildal W, Risberg B, Abeler VM, Kristensen GB, Sudbo J, Nesland JM, et al. beta-catenin expression, DNA ploidy and clinicopathological features in ovarian cancer: a study in 253 patients. Eur. J. Cancer. 2005; 41(8): 1127–1134.

    Article  PubMed  CAS  Google Scholar 

  66. Wu R, Zhai Y, Fearon ER, Cho KR. Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer. Res. 2001; 61(22): 8247–8255.

    PubMed  CAS  Google Scholar 

  67. Karbova E, Davidson B, Metodiev K, Trope CG, Nesland JM. Adenomatous polyposis coli (APC) protein expression in primary and metastatic serous ovarian carcinoma. Int. J. Surg. Pathol. 2002; 10(3): 175–180.

    Article  PubMed  CAS  Google Scholar 

  68. Pan S, Cheng L, White JT, Lu W, Utleg AG, Yan X, et al. Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian Cancers. Omics 2009; 13(4): 345–354.

    Google Scholar 

  69. Ueda M, Gemmill RM, West J, Winn R, Sugita M, Tanaka N, et al. Mutations of the beta- and gamma-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas. Br. J. Cancer. 2001; 85(1): 64–68.

    Article  PubMed  CAS  Google Scholar 

  70. Soubry A, van Hengel J, Parthoens E, Colpaert C, Van Marck E, Waltregny D, et al. Expression and nuclear location of the transcriptional repressor Kaiso is regulated by the tumor microenvironment. Cancer. Res. 2005; 65(6): 2224–2233.

    Article  PubMed  CAS  Google Scholar 

  71. Pon YL, Auersperg N, Wong AS. Gonadotropins regulate N-cadherin-mediated human ovarian surface epithelial cell survival at both post-translational and transcriptional levels through a cyclic AMP/protein kinase A pathway. J. Biol. Chem. 2005; 280(15): 15438–15448.

    Article  PubMed  CAS  Google Scholar 

  72. Murdoch WJ. Programmed cell death in preovulatory ovine follicles. Biol. Reprod. 1995; 53(1): 8–12.

    Article  PubMed  CAS  Google Scholar 

  73. Reddy P, Liu L, Ren C, Lindgren P, Boman K, Shen Y, et al. Formation of E-cadherin-mediated cell-cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells. Mol. Endocrinol. 2005; 19(10): 2564–2578.

    Article  PubMed  CAS  Google Scholar 

  74. Ong A, Maines-Bandiera SL, Roskelley CD Auersperg N. An ovarian adenocarcinoma line derived from SV40/E-cadherin-transfected normal human ovarian surface epithelium. Int. J. Cancer. 2000; 85(3): 430–437.

    Article  PubMed  CAS  Google Scholar 

  75. Wu C, Cipollone J, Maines-Bandiera S, Tan C, Karsan A, Auersperg N, et al. The morphogenic function of E-cadherin-mediated adherens junctions in epithelial ovarian carcinoma formation and progression. Differentiation 2008; 76(2): 193–205.

    Article  PubMed  CAS  Google Scholar 

  76. Bullions LC, Notterman DA, Chung LS, Levine AJ. Expression of wild-type alpha-catenin protein in cells with a mutant alpha-catenin gene restores both growth regulation and tumor suppressor activities. Mol. Cell. Biol. 1997; 17(8): 4501–4508.

    PubMed  CAS  Google Scholar 

  77. Giannini AL, Vivanco M, Kypta RM. alpha-catenin inhibits beta-catenin signaling by preventing formation of a beta-catenin*T-cell factor*DNA complex. J. Biol. Chem. 2000; 275(29): 21883–21888.

    Article  PubMed  CAS  Google Scholar 

  78. Frankel A, Buckman R, Kerbel RS. Abrogation of taxol-induced G2-M arrest and apoptosis in human ovarian cancer cells grown as multicellular tumor spheroids. Cancer. Res. 1997; 57(12): 2388–2393.

    PubMed  CAS  Google Scholar 

  79. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Curr. Opin. Cell. Biol. 2003; 15(6): 740–746.

    Article  PubMed  CAS  Google Scholar 

  80. Veatch AL, Carson LF, Ramakrishnan S. Differential expression of the cell-cell adhesion molecule E-cadherin in ascites and solid human ovarian tumor cells. Int. J. Cancer. 1994; 58(3): 393–399.

    Article  PubMed  CAS  Google Scholar 

  81. Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 1998; 392(6672): 190–193.

    Article  PubMed  CAS  Google Scholar 

  82. Risinger JI, Berchuck A, Kohler MF Boyd J. Mutations of the E-cadherin gene in human gynecologic cancers. Nat. Genet. 1994; 7(1): 98–102.

    Article  PubMed  CAS  Google Scholar 

  83. Yuecheng Y, Hongmei L, Xiaoyan X. Clinical evaluation of E-cadherin expression and its regulation mechanism in epithelial ovarian cancer. Clin. Exp. Metastasis. 2006; 23(1): 65–74.

    Article  PubMed  CAS  Google Scholar 

  84. Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR. Cadherin switching. J. Cell. Sci. 2008; 121(Pt 6): 727–735.

    Article  PubMed  CAS  Google Scholar 

  85. Zeineldin R, Rosenberg M, Ortega D, Buhr C, Chavez MG, Stack MS, et al. Mesenchymal transformation in epithelial ovarian tumor cells expressing epidermal growth factor receptor variant III. Mol. Carcinog. 2006; 45(11): 851–860.

    Article  PubMed  CAS  Google Scholar 

  86. Rosano L, Spinella F, Di Castro V, Nicotra MR, Dedhar S, de Herreros AG, et al. Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells. Cancer. Res. 2005; 65(24): 11649–11657.

    Article  PubMed  CAS  Google Scholar 

  87. Pon YL, Zhou HY, Cheung AN, Ngan HY, Wong AS. p70 S6 kinase promotes epithelial to mesenchymal transition through snail induction in ovarian cancer cells. Cancer. Res. 2008; 68(16): 6524–6532.

    Article  PubMed  CAS  Google Scholar 

  88. Colomiere M, Ward AC, Riley C, Trenerry MK, Cameron-Smith D, Findlay J, et al. Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br. J. Cancer. 2009; 100(1): 134–144.

    Article  PubMed  CAS  Google Scholar 

  89. Ahmed N, Thompson EW, Quinn MA. Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: an exception to the norm. J. Cell. Physiol. 2007; 213(3): 581–588.

    Article  PubMed  CAS  Google Scholar 

  90. Huang RY, Wang SM, Hsieh CY, Wu JC. Lysophosphatidic acid induces ovarian cancer cell dispersal by activating Fyn kinase associated with p120-catenin. Int. J. Cancer. 2008; 123(4): 801–809.

    Article  PubMed  CAS  Google Scholar 

  91. Sawada K, Mitra AK, Radjabi AR, Bhaskar V, Kistner EO, Tretiakova M, et al. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer. Res. 2008; 68(7): 2329–2339.

    Article  PubMed  CAS  Google Scholar 

  92. Hu L, Ferrara N, Jaffe RB. Paracrine VEGF/VE-cadherin action on ovarian cancer permeability. Exp. Biol. Med. (Maywood) 2006; 231(10): 1646–1652.

    CAS  Google Scholar 

  93. Pon YL, Wong AS. Gonadotropin-induced apoptosis in human ovarian surface epithelial cells is associated with cyclooxygenase-2 up-regulation via the beta-catenin/T-cell factor signaling pathway. Mol. Endocrinol. 2006; 20(12): 3336–3350.

    Article  PubMed  CAS  Google Scholar 

  94. Rosano L, Cianfrocca R, Masi S, Spinella F, Di Castro V, Biroccio A, et al. Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis. Proc. Natl. Acad. Sci. USA 2009; 106(8): 2806–2811.

    Article  PubMed  CAS  Google Scholar 

  95. Bourguignon LY, Peyrollier K, Gilad E, Brightman A. Hyaluronan-CD44 interaction with neural Wiskott-Aldrich syndrome protein (N-WASP) promotes actin polymerization and ErbB2 activation leading to beta-catenin nuclear translocation, transcriptional up-regulation, and cell migration in ovarian tumor cells. J. Biol. Chem. 2007; 282(2): 1265–1280.

    Article  PubMed  CAS  Google Scholar 

  96. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, et al. Identification of c-MYC as a target of the APC pathway. Science 1998; 281(5382): 1509–1512.

    Article  PubMed  CAS  Google Scholar 

  97. Schwartz DR, Wu R, Kardia SL, Levin AM, Huang CC, Shedden KA, et al. Novel candidate targets of beta-catenin/T-cell factor signaling identified by gene expression profiling of ovarian endometrioid adenocarcinomas. Cancer. Res. 2003; 63(11): 2913–2922.

    PubMed  CAS  Google Scholar 

  98. Bobek LA, Aguirre A, Levine MJ. Human salivary cystatin S. Cloning, sequence analysis, hybridization in situ and immunocytochemistry. Biochem. J. 1991; 278(Pt 3): 627–635.

    PubMed  CAS  Google Scholar 

  99. Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc. Natl. Acad. Sci. USA 1989; 86(8): 2863–2867.

    Article  PubMed  CAS  Google Scholar 

  100. Hendrix ND, Wu R, Kuick R, Schwartz DR, Fearon ER, Cho KR. Fibroblast growth factor 9 has oncogenic activity and is a downstream target of Wnt signaling in ovarian endometrioid adenocarcinomas. Cancer. Res. 2006; 66(3): 1354–1362.

    Article  PubMed  CAS  Google Scholar 

  101. Thoreson MA, Anastasiadis PZ, Daniel JM, Ireton RC, Wheelock MJ, Johnson KR, et al. Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. J. Cell. Biol. 2000; 148(1): 189–202.

    Article  PubMed  CAS  Google Scholar 

  102. Anastasiadis PZ, Reynolds AB. The p120 catenin family: complex roles in adhesion, signaling and cancer. J. Cell. Sci. 2000; 113(Pt 8): 1319–1334.

    PubMed  CAS  Google Scholar 

  103. Zhuge Y, Xu J. Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion across collagen barrier. J. Biol. Chem. 2001; 276(19): 16248–16256.

    PubMed  CAS  Google Scholar 

  104. Engers R, Springer E, Michiels F, Collard JG, Gabbert HE. Rac affects invasion of human renal cell carcinomas by up-regulating tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 expression. J. Biol. Chem. 2001; 276(45): 41889–41897.

    Article  PubMed  CAS  Google Scholar 

  105. Daniel JM, Reynolds AB. The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol. Cell. Biol. 1999; 19(5): 3614–3623.

    PubMed  CAS  Google Scholar 

  106. Spring CM, Kelly KF, O’Kelly I, Graham M, Crawford HC, Daniel JM. The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin. Exp. Cell. Res. 2005; 305(2): 253–265.

    Article  PubMed  CAS  Google Scholar 

  107. Park JI, Kim SW, Lyons JP, Ji H, Nguyen TT, Cho K, et al. Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets. Dev. Cell. 2005; 8(6): 843–854.

    Article  PubMed  CAS  Google Scholar 

  108. Takahashi K, Suzuki K. Density-dependent inhibition of growth involves prevention of EGF receptor activation by E-cadherin-mediated cell-cell adhesion. Exp. Cell. Res. 1996; 226(1): 214–222.

    Article  PubMed  CAS  Google Scholar 

  109. Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C, Dejana E. Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J. Cell. Biol. 2006; 174(4): 593–604.

    Article  PubMed  CAS  Google Scholar 

  110. Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, et al. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 1999; 98(2): 147–157.

    Article  PubMed  CAS  Google Scholar 

  111. De Santis G, Miotti S, Mazzi M, Canevari S, Tomassetti A. E-cadherin directly contributes to PI3K/AKT activation by engaging the PI3K-p85 regulatory subunit to adherens junctions of ovarian carcinoma cells. Oncogene 2009; 28(9): 1206–1217.

    Article  PubMed  CAS  Google Scholar 

  112. Ouban A, Muraca P, Yeatman T, Coppola D. Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas. Hum. Pathol. 2003; 34(8): 803–808.

    Article  PubMed  CAS  Google Scholar 

  113. Spentzos D, Cannistra SA, Grall F, Levine DA, Pillay K, Libermann TA, et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocr. Relat. Cancer. 2007; 14(3): 781–790.

    Article  PubMed  CAS  Google Scholar 

  114. Park SH, Cheung LW, Wong AS, Leung PC. Estrogen regulates Snail and Slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor alpha. Mol. Endocrinol. 2008; 22(9): 2085–2098.

    Article  PubMed  CAS  Google Scholar 

  115. Feldkamper M, Enderle-Schmitt U, Hackenberg R, Schulz KD. Urinary excretion of growth factors in patients with ovarian cancer. Eur. J. Cancer. 1994; 30A(12): 1851–1858.

    Article  PubMed  CAS  Google Scholar 

  116. Ridderheim M, Cajander S, Tavelin B, Stendahl U, Backstrom T. EGF/TGF-alpha and progesterone in urine of ovarian cancer patients. Anticancer. Res. 1994; 14(5B): 2119–2123.

    PubMed  CAS  Google Scholar 

  117. Baron AT, Lafky JM, Boardman CH, Balasubramaniam S, Suman VJ, Podratz KC, et al. Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer. Cancer. Epidemiol. Biomarkers. Prev. 1999; 8(2): 129–137.

    PubMed  CAS  Google Scholar 

  118. Bartlett JM, Langdon SP, Simpson BJ, Stewart M, Katsaros D, Sismondi P, et al. The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. Br. J. Cancer. 1996; 73(3): 301–306.

    Article  PubMed  CAS  Google Scholar 

  119. Niikura H, Sasano H, Sato S, Yajima A. Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors. Int. J. Gynecol. Pathol. 1997; 16(1): 60–68.

    Article  PubMed  CAS  Google Scholar 

  120. Sowter HM, Corps AN, Smith SK. Hepatocyte growth factor (HGF) in ovarian epithelial tumour fluids stimulates the migration of ovarian carcinoma cells. Int. J. Cancer. 1999; 83(4): 476–480.

    Article  PubMed  CAS  Google Scholar 

  121. Baykal C, Demirtas E, Al A, Ayhan A, Yuce K, Tulunay G, et al. Comparison of HGF (hepatocyte growth factor) levels of epithelial ovarian cancer cyst fluids with benign ovarian cysts. Int. J. Gynecol. Cancer. 2003; 13(6): 771–775.

    Article  PubMed  CAS  Google Scholar 

  122. Bagnato A, Salani D, Di Castro V, Wu-Wong JR, Tecce R, Nicotra MR, et al. Expression of endothelin 1 and endothelin A receptor in ovarian carcinoma: evidence for an autocrine role in tumor growth. Cancer. Res. 1999; 59(3): 720–727.

    PubMed  CAS  Google Scholar 

  123. Di Renzo MF, Olivero M, Giacomini A, Porte H, Chastre E, Mirossay L, et al. Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer. Clin. Cancer. Res. 1995; 1(2): 147–154.

    PubMed  Google Scholar 

  124. Huntsman D, Resau JH, Klineberg E, Auersperg N. Comparison of c-met expression in ovarian epithelial tumors and normal epithelia of the female reproductive tract by quantitative laser scan microscopy. Am. J. Pathol. 1999; 155(2): 343–348.

    Article  PubMed  CAS  Google Scholar 

  125. Sawada K, Radjabi AR, Shinomiya N, Kistner E, Kenny H, Becker AR, et al. c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion. Cancer. Res. 2007; 67(4): 1670–1679.

    Article  PubMed  CAS  Google Scholar 

  126. Imai T, Horiuchi A, Wang C, Oka K, Ohira S, Nikaido T, et al. Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. Am. J. Pathol. 2003; 163(4): 1437–1447.

    Article  PubMed  CAS  Google Scholar 

  127. Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell. Biol. 2000; 2(2): 84–89.

    Article  PubMed  CAS  Google Scholar 

  128. Kurrey, NK, Amit K, Bapat SA. Snail and Slug are major determinants of ovarian cancer invasiveness at the transcription level. Gynecol. Oncol. 2005; 97(1): 155–165.

    Article  PubMed  CAS  Google Scholar 

  129. Elloul S, Elstrand MB, Nesland JM, Trope CG, Kvalheim G, Goldberg I, et al. Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer 2005; 103(8): 1631–1643.

    Article  PubMed  CAS  Google Scholar 

  130. Elloul S, Silins I, Trope CG, Benshushan A, Davidson B, Reich R. Expression of E-cadherin transcriptional regulators in ovarian carcinoma. Virchows. Arch. 2006; 449(5): 520–528.

    Article  PubMed  CAS  Google Scholar 

  131. Terauchi M, Kajiyama H, Yamashita M, Kato M, Tsukamoto H, Umezu T, et al. Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma. Clin. Exp. Metastasis. 2007; 24(5): 329–339.

    Article  PubMed  CAS  Google Scholar 

  132. Hosono S, Kajiyama H, Terauchi M, Shibata K, Ino K, Nawa A, et al. Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients. Br. J. Cancer. 2007; 96(2): 314–320.

    Article  PubMed  CAS  Google Scholar 

  133. Blechschmidt K, Sassen S, Schmalfeldt B, Schuster T, Hofler H, Becker KF. The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients. Br. J. Cancer. 2008; 98(2): 489–495.

    Article  PubMed  CAS  Google Scholar 

  134. Sundfeldt K, Ivarsson K, Rask K, Haeger M, Hedin L, Brannstrom M. Higher levels of soluble E-cadherin in cyst fluid from malignant ovarian tumours than in benign cysts. Anticancer. Res. 2001; 21(1A): 65–70.

    PubMed  CAS  Google Scholar 

  135. Symowicz J, Adley BP, Gleason KJ, Johnson JJ, Ghosh S, Fishman DA, et al. Engagement of collagen-binding integrins promotes matrix metalloproteinase-9-dependent E-cadherin ectodomain shedding in ovarian carcinoma cells. Cancer. Res. 2007; 67(5): 2030–2039.

    Article  PubMed  CAS  Google Scholar 

  136. Cowden Dahl KD, Symowicz J, Ning Y, Gutierrez E, Fishman DA, Adley BP, et al. Matrix metalloproteinase 9 is a mediator of epidermal growth factor-dependent e-cadherin loss in ovarian carcinoma cells. Cancer. Res. 2008; 68(12): 4606–4613.

    Article  PubMed  CAS  Google Scholar 

  137. Gil OD, Lee C, Ariztia EV, Wang FQ, Smith PJ, Hope JM, et al. Lysophosphatidic acid (LPA) promotes E-cadherin ectodomain shedding and OVCA429 cell invasion in an uPA-dependent manner. Gynecol. Oncol. 2008; 108(2): 361–369.

    Article  PubMed  CAS  Google Scholar 

  138. Emons G, Pahwa GS, Brack C, Sturm R, Oberheuser F, Knuppen R. Gonadotropin releasing hormone binding sites in human epithelial ovarian carcinomata. Eur. J. Cancer. Clin. Oncol. 1989; 25(2): 215–221.

    Article  PubMed  CAS  Google Scholar 

  139. Irmer G, Burger C, Muller R, Ortmann O, Peter U, Kakar SS, et al. Expression of the messenger RNAs for luteinizing hormone-releasing hormone (LHRH) and its receptor in human ovarian epithelial carcinoma. Cancer. Res. 1995; 55(4): 817–822.

    PubMed  CAS  Google Scholar 

  140. Chien CH, Chen CH, Lee CY, Chang TC, Chen RJ, Chow SN. Detection of gonadotropin-releasing hormone receptor and its mRNA in primary human epithelial ovarian cancers. Int. J. Gynecol. Cancer. 2004; 14(3): 451–458.

    Article  PubMed  Google Scholar 

  141. Perotti A, Sessa C, Mancuso A, Noberasco C, Cresta S, Locatelli A, et al. Clinical and pharmacological phase I evaluation of Exherin (ADH-1), a selective anti-N-cadherin peptide in patients with N-cadherin-expressing solid tumours. Ann. Oncol. 2009; 20(4): 741–745.

    Article  PubMed  CAS  Google Scholar 

  142. Kelland L. Drug evaluation: ADH-1, an N-cadherin antagonist targeting cancer vascularization. Curr. Opin. Mol. Ther. 2007; 9(1): 86–91.

    PubMed  CAS  Google Scholar 

  143. Gupta M, Barnes D, Losos J, Spehar G, Bednarcik M, Peters WP. Anti-tumor activity of ADH-1 in vitro and in vivo in combination with paclitaxel in ovarian cancer cell lines. in American Society of Clinical Oncology Annual Meeting. J. Clin. Oncol. 2007; 25(18S): 16050.

    Google Scholar 

  144. Huang YH, Bao Y, Peng W, Goldberg M, Love K, Bumcrot DA, et al. Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis. Proc. Natl. Acad. Sci. USA 2009; 106(9): 3426–3430.

    Article  PubMed  CAS  Google Scholar 

  145. Landen CN, Merritt WM, Mangala LS, Sanguino AM, Bucana C, Lu C, et al. Intraperitoneal delivery of liposomal siRNA for therapy of advanced ovarian cancer. Cancer. Biol. Ther. 2006; 5(12): 1708–1713.

    Article  PubMed  CAS  Google Scholar 

  146. Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, et al. microRNAs exhibit high frequency genomic alterations in human cancer. Proc. Natl. Acad. Sci. USA 2006; 103(24): 9136–9141.

    Article  PubMed  CAS  Google Scholar 

  147. Gregory RI Shiekhattar R. MicroRNA biogenesis and cancer. Cancer. Res. 2005; 65(9): 3509–3512.

    Article  PubMed  CAS  Google Scholar 

  148. 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  PubMed  CAS  Google Scholar 

  149. 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  CAS  Google Scholar 

  150. Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK. MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol. Cancer. Ther. 2009; 8(5): 1055–1066.

    Google Scholar 

Download references

Acknowledgments

This work was supported by Hong Kong Research Grant Council grants 7599/05 M and 778108 and by HKU Outstanding Young Researcher Award (to A.S.T Wong).

Author information

Authors and Affiliations

  1. School of Biological Sciences, University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong

    Lydia W.T. Cheung & Carman K.M. Ip

  2. School of Biological Sciences, University of Hong Kong, 4S-14 Kadoorie Biological Sciences Building, Pokfulam Road, Pokfulam, Hong Kong

    Alice S.T. Wong

Authors
  1. Lydia W.T. Cheung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carman K.M. Ip
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alice S.T. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alice S.T. Wong .

Editor information

Editors and Affiliations

  1. Tzu-Chi University, College of Medicine, Institute of medical biotechnology, Chung-Yang Rd, Sec 3 701, Hualien, 970, Taiwan R.O.C.

    Wen-Sheng Wu

  2. Buddhist Tzu-Chi General Hospital, Department of Medicine, Research Center for Hepatology, Chung-Yang Rd, Sec 3 707, Hualien, 970, Taiwan R.O.C.

    Chi-Tan Hu

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Cheung, L.W., Ip, C.K., Wong, A.S. (2010). Cadherin-Catenin Signaling in Ovarian Cancer Progression. In: Wu, WS., Hu, CT. (eds) Signal Transduction in Cancer Metastasis. Cancer Metastasis - Biology and Treatment, vol 15. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9522-0_12

Download citation

Publish with us

Policies and ethics

Search

Navigation