Archives of Gynecology and Obstetrics

, Volume 297, Issue 1, pp 161–183 | Cite as

Identification of differentially expressed genes regulated by molecular signature in breast cancer-associated fibroblasts by bioinformatics analysis

  • Basavaraj Vastrad
  • Chanabasayya Vastrad
  • Anandkumar Tengli
  • Sudhir Iliger
Gynecologic Oncology



Breast cancer is a severe risk to public health and has adequately convoluted pathogenesis. Therefore, the description of key molecular markers and pathways is of much importance for clarifying the molecular mechanism of breast cancer-associated fibroblasts initiation and progression. Breast cancer-associated fibroblasts gene expression dataset was downloaded from Gene Expression Omnibus database.


A total of nine samples, including three normal fibroblasts, three granulin-stimulated fibroblasts and three cancer-associated fibroblasts samples, were used to identify differentially expressed genes (DEGs) between normal fibroblasts, granulin-stimulated fibroblasts and cancer-associated fibroblasts samples. The gene ontology (GO) and pathway enrichment analysis was performed, and protein-protein interaction (PPI) network of the DEGs was constructed by NetworkAnalyst software.


Totally, 190 DEGs were identified, including 66 up-regulated and 124 down-regulated genes. GO analysis results showed that up-regulated DEGs were significantly enriched in biological processes (BP), including cell-cell signalling and negative regulation of cell proliferation; molecular function (MF), including insulin-like growth factor II binding and insulin-like growth factor I binding; cellular component (CC), including insulin-like growth factor binding protein complex and integral component of plasma membrane; the down-regulated DEGs were significantly enriched in BP, including cell adhesion and extracellular matrix organization; MF, including N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase activity and calcium ion binding; CC, including extracellular space and extracellular matrix. WIKIPATHWAYS analysis showed the up-regulated DEGs were enriched in myometrial relaxation and contraction pathways. WIKIPATHWAYS, REACTOME, PID_NCI and KEGG pathway analysis showed the down-regulated DEGs were enriched endochondral ossification, TGF beta signalling pathway, integrin cell surface interactions, beta1 integrin cell surface interactions, malaria and glycosaminoglycan biosynthesis—chondroitin sulfate/dermatan sulphate. The top 5 up-regulated hub genes, CDKN2A, MME, PBX1, IGFBP3, and TFAP2C and top 5 down-regulated hub genes VCAM1, KRT18, TGM2, ACTA2, and STAMBP were identified from the PPI network, and subnetworks revealed these genes were involved in significant pathways, including myometrial relaxation and contraction pathways, integrin cell surface interactions, beta1 integrin cell surface interaction. Besides, the target hsa-mirs for DEGs were identified. hsa-mir-759, hsa-mir-4446-5p, hsa-mir-219a-1-3p and hsa-mir-26a-5p were important miRNAs in this study.


We pinpoint important key genes and pathways closely related with breast cancer-associated fibroblasts initiation and progression by a series of bioinformatics analysis on DEGs. These screened genes and pathways provided for a more detailed molecular mechanism underlying breast cancer-associated fibroblasts occurrence and progression, holding promise for acting as molecular markers and probable therapeutic targets.


Differentially expressed gene Gene ontology Fibroblasts Protein-protein interaction 



We thank Marsh T., very much, the author who deposited their microarray dataset, GSE75333, into the public Gene Expression Omnibus (GEO) database.

Author contributions

BV carried out the design of this study, performed the statistical analysis and drafted the manuscript. CV collected important background information and software. AKT and SI participated in its design and coordination, visualizations and also helped to draft the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

No informed consent because this study does not contain human or animals participants.


  1. 1.
    Jung YY, Kim HM, Koo JS (2016) The role of cancer-associated fibroblasts in breast cancer pathobiology. Histol Histopathol 31(4):371–378. doi: 10.14670/HH-11-700 PubMedGoogle Scholar
  2. 2.
    Luo H, Tu G, Liu Z, Liu M (2015) Cancer-associated fibroblasts: a multifaceted driver of breast cancer progression. Cancer Lett 361(2):155–163. doi: 10.1016/j.canlet.2015.02.018 PubMedCrossRefGoogle Scholar
  3. 3.
    Qiao A, Gu F, Guo X, Zhang X, Fu L (2016) Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications. Front Med 10(1):33–40. doi: 10.1007/s11684-016-0431-5 PubMedCrossRefGoogle Scholar
  4. 4.
    Sugimoto H, Mundel TM, Kieran MW, Kalluri R (2006) Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther 5(12):1640–1646PubMedCrossRefGoogle Scholar
  5. 5.
    Pasanen I, Lehtonen S, Sormunen R, Skarp S, Lehtilahti E, Pietilä M, Sequeiros RB, Lehenkari P, Kuvaja P (2016) Breast cancer carcinoma-associated fibroblasts differ from breast fibroblasts in immunological and extracellular matrix regulating pathways. Exp Cell Res 344(1):53–66. doi: 10.1016/j.yexcr.2016.04.016 PubMedCrossRefGoogle Scholar
  6. 6.
    Sappino AP, Skalli O, Jackson B, Schürch W, Gabbiani G (1998) Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues. Int J Cancer 41(5):707–712CrossRefGoogle Scholar
  7. 7.
    Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9(4):265–273. doi: 10.1038/nrc2620 PubMedCrossRefGoogle Scholar
  8. 8.
    Weber CE, Kothari AN, Wai PY, Li NY, Driver J, Zapf MA, Franzen CA, Gupta GN, Osipo C, Zlobin A, Syn WK, Zhang J, Kuo PC, Mi Z (2015) Osteopontin mediates an MZF1-TGF-β1-dependent transformation of mesenchymal stem cells into cancer associated fibroblasts in breast cancer. Oncogene 34(37):4821–4833. doi: 10.1038/onc.2014.410 PubMedCrossRefGoogle Scholar
  9. 9.
    Rønnov-Jessen L, Petersen OW, Koteliansky VE, Bissell MJ (1995) The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. J Clin Investig 95(2):859–873PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Paulsson J, Sjöblom T, Micke P, Pontén F, Landberg G, Heldin CH, Bergh J, Brennan DJ, Jirström K, Ostman A (2009) Prognostic significance of stromal platelet-derived growth factor beta-receptor expression in human breast cancer. Am J Pathol 175(1):334–341. doi: 10.2353/ajpath.2009.081030 PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    El-Gendi SM, Mostafa MF, El-Gendi AM (2012) Stromal caveolin-1 expression in breast carcinoma. Correlation with early tumor recurrence and clinical outcome. Pathol Oncol Res 18(2):459–469. doi: 10.1007/s12253-011-9469-5 PubMedCrossRefGoogle Scholar
  12. 12.
    Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109(9):1721–1728. doi: 10.1002/cncr.22618 PubMedCrossRefGoogle Scholar
  13. 13.
    Huo D, Ikpatt F, Khramtsov A, Dangou JM, Nanda R, Dignam J, Zhang B, Grushko T, Zhang C, Oluwasola O, Malaka D, Malami S, Odetunde A, Adeoye AO, Iyare F, Falusi A, Perou CM, Olopade OI (2009) Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. J Clin Oncol 27(27):4515–4521. doi: 10.1200/JCO.2008.19.6873 PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281. doi: 10.1200/JCO.2007.14.4147 PubMedCrossRefGoogle Scholar
  15. 15.
    O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C (2011) Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 364(3):205–214. doi: 10.1056/NEJMoa1011418 PubMedCrossRefGoogle Scholar
  16. 16.
    Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109(1):25–32. doi: 10.1002/cncr.22381 PubMedCrossRefGoogle Scholar
  17. 17.
    Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz AL, Brisken C, Fiche M, Delorenzi M, Iggo R (2005) Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24(29):4660–4671. doi: 10.1038/sj.onc.1208561 PubMedCrossRefGoogle Scholar
  18. 18.
    Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genom 7:96. doi: 10.1186/1471-2164-7-96 CrossRefGoogle Scholar
  19. 19.
    Lal S, McCart Reed AE, de Luca XM, Simpson PT (2017) Molecular signatures in breast cancer. Methods S1046–2023(17):30058. doi: 10.1016/j.ymeth.2017.06.032 Google Scholar
  20. 20.
    Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ (2007) Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 9(5):R65. doi: 10.1186/bcr1771 PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Marsh T, Wong I, Sceneay J, Barakat A, Qin Y, Sjödin A, Alspach E, Nilsson B, Stewart SA, McAllister SS (2016) Hematopoietic age at onset of triple-negative breast cancer dictates disease aggressiveness and progression. Cancer Res 76(10):2932–2943. doi: 10.1158/0008-5472.CAN-15-3332 PubMedCrossRefGoogle Scholar
  22. 22.
    Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) Affy analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315. doi: 10.1093/bioinformatics/btg405 PubMedCrossRefGoogle Scholar
  23. 23.
    Smyth GK (2005) LIMMA: linear models for microarray data. Bioinformatics and computational biology solutions using R and Bioconductor. Springer, New York, pp 397–420CrossRefGoogle Scholar
  24. 24.
    Efron B, Tibshirani R (2002) Empirical Bayes methods and false discovery rates for microarrays. Genet Epidemiol 23(1):70–86. doi: 10.1002/gepi.1124 PubMedCrossRefGoogle Scholar
  25. 25.
    Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25(1):25–29. doi: 10.1038/75556 PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Sulakhe D, Balasubramanian S, Xie B, Feng B, Taylor A, Wang S, Berrocal E, Dave U, Xu J, Börnigen D, Gilliam TC, Maltsev N (2014) Lynx: a database and knowledge extraction engine for integrative medicine. Nucleic Acids Res 42(Database issue):D1007–D1112. doi: 10.1093/nar/gkt1166 PubMedCrossRefGoogle Scholar
  27. 27.
    Kelder T, van Iersel MP, Hanspers K, Kutmon M, Conklin BR, Evelo CT, Pico AR (2012) WikiPathways: building research communities on biological pathways. Nucleic Acids Res 40(Database issue):D1301–D1307. doi: 10.1093/nar/gkr1074 PubMedCrossRefGoogle Scholar
  28. 28.
    D’Eustachio P (2011) Reactome knowledgebase of human biological pathways and processes. Methods Mol Biol 694:49–61. doi: 10.1007/978-1-60761-977-2_4 PubMedCrossRefGoogle Scholar
  29. 29.
    Schaefer CF, Anthony K, Krupa S, Buchoff J, Day M, Hannay T, Buetow KH (2009) PID: the pathway interaction database. Nucleic Acids Res 37(Database issue):D674–D679. doi: 10.1093/nar/gkn653 PubMedCrossRefGoogle Scholar
  30. 30.
    Minoru K, Susumu G (2000) KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 28(1):27–30. doi: 10.1093/nar/28.1.27 CrossRefGoogle Scholar
  31. 31.
    Xia J, Gill EE, Hancock RE (2015) NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data. Nat Protoc 10(6):823–844. doi: 10.1038/nprot.2015.052 PubMedCrossRefGoogle Scholar
  32. 32.
    Breuer K, Foroushani AK, Laird MR, Chen C, Sribnaia A, Lo R, Winsor GL, Hancock RE, Brinkman FS, Lynn DJ (2013) InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curation. Nucleic Acids Res 41(Database issue):D1228–D1233. doi: 10.1093/nar/gks1147 PubMedCrossRefGoogle Scholar
  33. 33.
    Vlachos IS, Paraskevopoulou MD, Karagkouni D, Georgakilas G, Vergoulis T, Kanellos I, Anastasopoulos IL, Maniou S, Karathanou K, Kalfakakou D, Fevgas A, Dalamagas T, Hatzigeorgiou AG (2015) DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions. Nucleic Acids Res 43(Database issue):D153–D159. doi: 10.1093/nar/gku1215 PubMedCrossRefGoogle Scholar
  34. 34.
    Finn RS, Dering J, Ginther C, Wilson CA, Glaspy P, Tchekmedyian N, Slamon DJ (2007) Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/”triple-negative” breast cancer cell lines growing in vitro. Breast Cancer Res Treat 105(3):319–326. doi: 10.1007/s10549-006-9463-x PubMedCrossRefGoogle Scholar
  35. 35.
    Smirnov DA, Foulk BW, Doyle GV, Connelly MC, Terstappen LW, O’Hara SM (2006) Global gene expression profiling of circulating endothelial cells in patients with metastatic carcinomas. Cancer Res 66(6):2918–2922. doi: 10.1158/0008-5472.CAN-05-4003 PubMedCrossRefGoogle Scholar
  36. 36.
    da Motta LL, Ledaki I, Purshouse K, Haider S, De Bastiani MA, Baban D, Morotti M, Steers G, Wigfield S, Bridges E, Li JL, Knapp S, Ebner D, Klamt F, Harris AL, McIntyre A (2017) The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene 36(1):122–132. doi: 10.1038/onc.2016.184 PubMedCrossRefGoogle Scholar
  37. 37.
    Haque I, Banerjee S, Mehta S, De A, Majumder M, Mayo MS, Kambhampati S, Campbell DR, Banerjee SK (2011) Cysteine-rich 61-connective tissue growth factor-nephroblastoma-overexpressed 5 (CCN5)/Wnt-1-induced signaling protein-2 (WISP-2) regulates microRNA-10b via hypoxia-inducible factor-1α-TWIST signaling networks in human breast cancer cells. J Biol Chem 286(50):43475–43485. doi: 10.1074/jbc.M111.284158 PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Santagata S, Thakkar A, Ergonul A, Wang B, Woo T, Hu R, Harrell JC, McNamara G, Schwede M, Culhane AC, Kindelberger D, Rodig S, Richardson A, Schnitt SJ, Tamimi RM, Ince TA (2014) Taxonomy of breast cancer based on normal cell phenotype predicts outcome. J Clin Investig 124(2):859–870. doi: 10.1172/JCI70941 PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Woodfield GW, Horan AD, Chen Y, Weigel RJ (2007) TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling. Cancer Res 67(18):8439–8443. doi: 10.1158/0008-5472.CAN-07-2293 PubMedCrossRefGoogle Scholar
  40. 40.
    He DX, Gu F, Gao F, Hao JJ, Gong D, Gu XT, Mao AQ, Jin J, Fu L, Ma X (2016) Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer. Sci Rep 6:24706. doi: 10.1038/srep24706 PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64(2):327–336PubMedCrossRefGoogle Scholar
  42. 42.
    Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC, Mills GB, Lau CC, Brown PH (2015) Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 21(7):1688–1698. doi: 10.1158/1078-0432.CCR-14-0432 PubMedCrossRefGoogle Scholar
  43. 43.
    Sargen MR, Merrill SL, Chu EY, Nathanson KL (2016) CDKN2A mutations with p14 loss predisposing to multiple nerve sheath tumours, melanoma, dysplastic naevi and internal malignancies: a case series and review of the literature. Br J Dermatol 175(4):785–789. doi: 10.1111/bjd.14485 PubMedCrossRefGoogle Scholar
  44. 44.
    Suzuki H, Zhou X, Yin J, Lei J, Jiang HY, Suzuki Y, Chan T, Hannon GJ, Mergner WJ, Abraham JM (1995) Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers. Hum Mol Genet 4(10):1883–1887PubMedCrossRefGoogle Scholar
  45. 45.
    Branham MT, Marzese DM, Laurito SR, Gago FE, Orozco JI, Tello OM, Vargas-Roig LM, Roqué M (2012) Methylation profile of triple-negative breast carcinomas. Oncogenesis 1:e17. doi: 10.1038/oncsis.2012.17 PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363(9418):1346–1353PubMedCrossRefGoogle Scholar
  47. 47.
    Key TJ, Appleby PN, Reeves GK, Roddam AW (2010) Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 11(6):530–542. doi: 10.1016/S1470-2045(10)70095-4 PubMedCrossRefGoogle Scholar
  48. 48.
    Liu AY, Cai Y, Mao Y, Lin Y, Zheng H, Wu T, Huang Y, Fang X, Lin S, Feng Q, Huang Z, Yang T, Luo Q, Ouyang G (2014) Twist2 promotes self-renewal of liver cancer stem-like cells by regulating CD24. Carcinogenesis 35(3):537–545. doi: 10.1093/carcin/bgt364 PubMedCrossRefGoogle Scholar
  49. 49.
    Fang X, Cai Y, Liu J, Wang Z, Wu Q, Zhang Z, Yang CJ, Yuan L, Ouyang G (2011) Twist2 contributes to breast cancer progression by promoting an epithelial–mesenchymal transition and cancer stem-like cell self-renewal. Oncogene 30(47):4707–4720. doi: 10.1038/onc.2011.181 PubMedCrossRefGoogle Scholar
  50. 50.
    Willrodt AH, Beffinger M, Vranova M, Protsyuk D, Schuler K, Jadhav M, Heikenwalder M, van den Broek M, Borsig L, Winter CH (2017) Stromal expression of activated leukocyte cell adhesion molecule (ALCAM) promotes lung tumor growth and metastasis. Am J Pathol S0002–9440(17):30330–30339. doi: 10.1016/j.ajpath.2017.07.008 Google Scholar
  51. 51.
    Kass L, Erler JT, Dembo M, Weaver VM (2017) Mammary epithelial cell: influence of extracellular matrix composition and organization during development and tumorigenesis. Int J Biochem Cell Biol 39(11):1987–1994. doi: 10.1016/j.biocel.2007.06.025 CrossRefGoogle Scholar
  52. 52.
    Carey L, Winer E, Viale G, Cameron D, Gianni L (2010) Triple-negative breast cancer: disease entity or title of convenience? Nat Rev Clin Oncol 7(12):683–692. doi: 10.1038/nrclinonc.2010.154 PubMedCrossRefGoogle Scholar
  53. 53.
    Tsuyada A, Chow A, Wu J, Somlo G, Chu P, Loera S, Luu T, Li AX, Wu X, Ye W, Chen S, Zhou W, Yu Y, Wang YZ, Ren X, Li H, Scherle P, Kuroki Y, Wang SE (2012) CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells. Cancer Res 72(11):2768–2779. doi: 10.1158/0008-5472.CAN-11-3567 PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Bonapace L, Coissieux MM, Wyckoff J, Mertz KD, Varga Z, Junt T, Bentires-Alj M (2014) Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature 515(7525):130–133. doi: 10.1038/nature13862 PubMedCrossRefGoogle Scholar
  55. 55.
    Gugnoni M, Sancisi V, Gandolfi G, Manzotti G, Ragazzi M, Giordano D, Tamagnini I, Tigano M, Frasoldati A, Piana S, Ciarrocchi A (2017) Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy. Oncogene 36(5):667–677. doi: 10.1038/onc.2016.237 PubMedCrossRefGoogle Scholar
  56. 56.
    Lourenço GJ, Cardoso-Filho C, Gonçales NS, Shinzato JY, Zeferino LC, Nascimento H, Costa FF, Gurgel MS, Lima CS (2006) A high risk of occurrence of sporadic breast cancer in individuals with the 104NN polymorphism of the COL18A1 gene. Breast Cancer Res Treat 100(3):335–338. doi: 10.1007/s10549-006-9259-z PubMedCrossRefGoogle Scholar
  57. 57.
    Vargas AC, McCart Reed AE, Waddell N, Lane A, Reid LE, Smart CE, Cocciardi S, da Silva L, Song S, Chenevix-Trench G, Simpson PT, Lakhani SR (2012) Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression. Breast Cancer Res Treat 135(1):153–165. doi: 10.1007/s10549-012-2123-4 PubMedCrossRefGoogle Scholar
  58. 58.
    Neidhart M, Müller-Ladner U, Frey W, Bosserhoff AK, Colombani PC, Frey-Rindova P, Hummel KM, Gay RE, Häuselmann H, Gay S (2000) Increased serum levels of non-collagenous matrix proteins (cartilage oligomeric matrix protein and melanoma inhibitory activity) in marathon runners. Osteoarthritis Cartil 8(3):222–229. doi: 10.1053/joca.1999.0293 CrossRefGoogle Scholar
  59. 59.
    Schrader AJ, Lechner O, Templin M, Dittmar KE, Machtens S, Mengel M, Probst-Kepper M, Franzke A, Wollensak T, Gatzlaff P, Atzpodien J, Buer J, Lauber J (2002) CXCR4/CXCL12 expression and signalling in kidney cancer. Br J Cancer 86(8):1250–1256. doi: 10.1038/sj.bjc.6600221 PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Gil M, Seshadri M, Komorowski MP, Abrams SI, Kozbor D (2013) Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases. Proc Natl Acad Sci USA 110(14):E1291–E1300. doi: 10.1073/pnas.1220580110 PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Pérez-Gómez E, Del Castillo G, Juan Francisco S, López-Novoa JM, Bernabéu C, Quintanilla M (2010) The role of the TGF-β coreceptor endoglin in cancer. Sci World J 10:2367–2384. doi: 10.1100/tsw.2010.230 CrossRefGoogle Scholar
  62. 62.
    Adhemar LF, José Manuel L, Fernando CS (2010) Angiogenesis and breast cancer. J Oncol 10:576384–576391. doi: 10.1155/2010/576384 Google Scholar
  63. 63.
    Kinoshita T, Nohata N, Hanazawa T, Kikkawa N, Yamamoto N, Yoshino H, Itesako T, Enokida H, Nakagawa M, Okamoto Y, Seki N (2013) Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma. Br J Cancer 109(10):2636–2645. doi: 10.1038/bjc.2013.607 PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Klahan S, Wu MS, Hsi E, Huang CC, Hou MF, Chang WC (2014) Computational analysis of mRNA expression profiles identifies the ITG family and PIK3R3 as crucial genes for regulating triple negative breast cancer cell migration. Biomed Res Int 2014:536591. doi: 10.1155/2014/536591 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Johnson JP, Bar-Eli M, Jansen B, Markhof E (1997) Melanoma progression-associated glycoprotein MUC18/MCAM mediates homotypic cell adhesion through interaction with a heterophilic ligand. Int J Cancer 73(5):769–774PubMedCrossRefGoogle Scholar
  66. 66.
    Zeng Q, Li W, Lu D, Wu Z, Duan H, Luo Y, Feng J, Yang D, Fu L, Yan X (2012) CD146, an epithelial–mesenchymal transition inducer, is associated with triple-negative breast cancer. Proc Natl Acad Sci USA 109(4):1127–1132. doi: 10.1073/pnas.1111053108 PubMedCrossRefGoogle Scholar
  67. 67.
    Takahashi S, Kato K, Nakamura K, Nakano R, Kubota K, Hamada H (2011) Neural cell adhesion molecule 2 as a target molecule for prostate and breast cancer gene therapy. Cancer Sci 102(4):808–814. doi: 10.1111/j.1349-7006.2011.01855.x PubMedCrossRefGoogle Scholar
  68. 68.
    Cavallaro U, Christofori G (2004) Multitasking in tumor progression: signaling functions of cell adhesion molecules. Ann N Y Acad Sci 1014:58–66PubMedCrossRefGoogle Scholar
  69. 69.
    Struyk AF, Canoll PD, Wolfgang MJ, Rosen CL, D’Eustachio P, Salzer JL (1995) Cloning of neurotrimin defines a new subfamily of differentially expressed neural cell adhesion molecules. J Neurosci 15(3 Pt 2):2141–2156PubMedGoogle Scholar
  70. 70.
    Xie X, Ma L, Xi K, Zhang W, Fan D (2017) MicroRNA-183 suppresses neuropathic pain and expression of AMPA receptors by targeting mTOR/VEGF signaling pathway. Cell Physiol Biochem 41(1):181–192. doi: 10.1159/000455987 PubMedCrossRefGoogle Scholar
  71. 71.
    Newman S, Howarth KD, Greenman CD, Bignell GR, Tavaré S, Edwards PA (2013) The relative timing of mutations in a breast cancer genome. PLoS One 8(6):e64991. doi: 10.1371/journal.pone.0064991 PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Dallas MR, Chen SH, Streppel MM, Sharma S, Maitra A, Konstantopoulos K (2012) Sialofucosylated podocalyxin is a functional E- and L-selectin ligand expressed by metastaticpancreatic cancer cells. Am J Physiol Cell Physiol 303(6):C616–C624. doi: 10.1152/ajpcell.00149.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Castro NP, Fedorova-Abrams ND, Merchant AS, Rangel MC, Nagaoka T, Karasawa H, Klauzinska M, Hewitt SM, Biswas K, Sharan SK, Salomon DS (2015) Cripto-1 as a novel therapeutic target for triple negative breast cancer. Oncotarget 6(14):11910–11929. doi: 10.18632/oncotarget.4182 PubMedCrossRefGoogle Scholar
  74. 74.
    Liesenfeld M, Mosig S, Funke H, Jansen L, Runnebaum IB, Dürst M, Backsch C (2013) SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes. BMC Cancer 13:507. doi: 10.1186/1471-2407-13-507 PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Luis-Ravelo D, Antón I, Zandueta C, Valencia K, Ormazábal C, Martínez-Canarias S, Guruceaga E, Perurena N, Vicent S, De Las Rivas J, Lecanda F (2014) A gene signature of bone metastatic colonization sensitizes for tumor-induced osteolysis and predicts survival in lung cancer. Oncogene 33(43):5090–5099. doi: 10.1038/onc.2013.440 PubMedCrossRefGoogle Scholar
  76. 76.
    Drake PM, Schilling B, Niles RK, Prakobphol A, Li B, Jung K, Cho W, Braten M, Inerowicz HD, Williams K, Albertolle M, Held JM, Iacovides D, Sorensen DJ, Griffith OL, Johansen E, Zawadzka AM, Cusack MP, Allen S, Gormley M, Hall SC, Witkowska HE, Gray JW, Regnier F, Gibson BW, Fisher SJ (2012) Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers. J Proteome Res 11(4):2508–2520. doi: 10.1021/pr201206w PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Chen Q, Zhang XH, Massagué J (2011) Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 20(4):538–549. doi: 10.1016/j.ccr.2011.08.025 PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Wushou A, Jiang YZ, Hou J, Liu YR, Guo XM, Shao ZM (2015) Development of triple-negative breast cancer radiosensitive gene signature and validation based on transcriptome analysis. Breast Cancer Res Treat 154(1):57–62. doi: 10.1007/s10549-015-3611-0 PubMedCrossRefGoogle Scholar
  79. 79.
    Kumar S, Rao N, Ge R (2012) Emerging roles of ADAMTSs in angiogenesis and cancer. Cancers (Basel) 4(4):1252–1299. doi: 10.3390/cancers4041252 CrossRefGoogle Scholar
  80. 80.
    Alarmo EL, Kuukasjärvi T, Karhu R, Kallioniemi A (2007) A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7. Breast Cancer Res Treat 103(2):239–246. doi: 10.1007/s10549-006-9362-1 PubMedCrossRefGoogle Scholar
  81. 81.
    Cyr-Depauw C, Northey JJ, Tabariès S, Annis MG, Dong Z, Cory S, Hallett M, Rennhack JP, Andrechek ER, Siegel PM (2016) Chordin-like 1 suppresses bone morphogenetic protein 4-induced breast cancer cell migration and invasion. Mol Cell Biol 36(10):1509–1525. doi: 10.1128/MCB.00600-15 PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Chapman KB, Prendes MJ, Sternberg H, Kidd JL, Funk WD, Wagner J, West MD (2012) COL10A1 expression is elevated in diverse solid tumor types and is associated with tumor vasculature. Future Oncol 8(8):1031–1040. doi: 10.2217/fon.12.79 PubMedCrossRefGoogle Scholar
  83. 83.
    Yang F, Liu YH, Dong SY, Yao ZH, Lv L, Ma RM, Dai XX, Wang J, Zhang XH, Wang OC (2016) Co-expression networks revealed potential core lncRNAs in the triple-negative breast cancer. Gene. doi: 10.1016/j.gene.2016.07.002 Google Scholar
  84. 84.
    Wu YH, Chang TH, Huang YF, Huang HD, Chou CY (2014) COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer. Oncogene 33(26):3432–3440. doi: 10.1038/onc.2013.307 PubMedCrossRefGoogle Scholar
  85. 85.
    Kim Y, Kim J, Lee HD, Jeong J, Lee W, Lee KA (2013) Spectrum of EGFR gene copy number changes and KRAS gene mutation status in Korean triple negative breast cancer patients. PLoS One 8(10):e79014. doi: 10.1371/journal.pone.0079014 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Mathe A, Wong-Brown M, Morten B, Forbes JF, Braye SG, Avery-Kiejda KA, Scott RJ (2015) Novel genes associated with lymph node metastasis in triple negative breast cancer. Sci Rep 5:15832. doi: 10.1038/srep15832 PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Hou C, Yang Z, Kang Y, Zhang Z, Fu M, He A, Zhang Z, Liao W (2015) MiR-193b regulates early chondrogenesis by inhibiting the TGF-beta2 signaling pathway. FEBS Lett 589(9):1040–1047. doi: 10.1016/j.febslet.2015.02.017 PubMedCrossRefGoogle Scholar
  88. 88.
    Liu C, Louhimo R, Laakso M, Lehtonen R, Hautaniemi S (2015) Identification of sample-specific regulations using integrative network level analysis. BMC Cancer 15:319. doi: 10.1186/s12885-015-1265-2 PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Gho JW, Ip WK, Chan KY, Law PT, Lai PB, Wong N (2008) Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest. Cancer Res 68(16):6743–6751. doi: 10.1158/0008-5472.CAN-07-6469 PubMedCrossRefGoogle Scholar
  90. 90.
    Karagoz K, Sinha R, Arga KY (2015) Triple negative breast cancer: a multi-omics network discovery strategy for candidate targets and driving pathways. OMICS 19(2):115–130. doi: 10.1089/omi.2014.0135 PubMedCrossRefGoogle Scholar
  91. 91.
    Gill ZP, Perks CM, Newcomb PV, Holly JM (1997) Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J Biol Chem 272(41):25602–25607PubMedCrossRefGoogle Scholar
  92. 92.
    Voudouri K, Berdiaki A, Tzardi M, Tzanakakis GN, Nikitovic D (2015) Insulin-like growth factor and epidermal growth factor signaling in breast cancer cell growth: focus on endocrine resistant disease. Anal Cell Pathol (Amst) 2015:975495. doi: 10.1155/2015/975495 Google Scholar
  93. 93.
    Han B, Bhowmick N, Qu Y, Chung S, Giuliano AE, Cui X (2017) FOXC1: an emerging marker and therapeutic target for cancer. Oncogene 36(28):3957–3963. doi: 10.1038/onc.2017.48 PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, Stanford J, Cook RS, Arteaga CL (2013) TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Investig 123(3):1348–1358. doi: 10.1172/JCI65416 PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Oliveira-Ferrer L, Heßling A, Trillsch F, Mahner S, Milde-Langosch K (2015) Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer. Tumour Biol 36(11):9023–9030. doi: 10.1007/s13277-015-3652-3 PubMedCrossRefGoogle Scholar
  96. 96.
    Herman D, Leakey TI, Behrens A, Yao-Borengasser A, Cooney CA, Jousheghany F, Phanavanh B, Siegel ER, Safar AM, Korourian S, Kieber-Emmons T, Monzavi-Karbassi B (2015) CHST11 gene expression and DNA methylation in breast cancer. Int J Oncol 46(3):1243–1251. doi: 10.3892/ijo.2015.2828 PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Hirota S, Ito A, Nagoshi J, Takeda M, Kurata A, Takatsuka Y, Kohri K, Nomura S, Kitamura Y (1995) Expression of bone matrix protein messenger ribonucleic acids in human breast cancers. Possible involvement of osteopontin in development of calcifying foci. Lab Investig 72(1):64–69PubMedGoogle Scholar
  98. 98.
    Kenny HA, Leonhardt P, Ladanyi A, Yamada SD, Montag A, Im HK, Jagadeeswaran S, Shaw DE, Mazar AP, Lengyel E (2011) Targeting the urokinase plasminogen activator receptor inhibits ovarian cancer metastasis. Clin Cancer Res 17(3):459–471. doi: 10.1158/1078-0432.CCR-10-2258 PubMedCrossRefGoogle Scholar
  99. 99.
    Mali AV, Joshi AA, Hegde MV, Kadam ShS (2017) Enterolactone suppresses proliferation, migration and metastasis of MDA-MB-231 breast cancer cells through inhibition of uPA induced plasmin activation and MMPs-mediated ECM remodeling. Asian Pac J Cancer Prev 18(4):905–915. doi: 10.22034/APJCP.2017.18.4.905 PubMedPubMedCentralGoogle Scholar
  100. 100.
    Nishina S, Shiraha H, Nakanishi Y, Tanaka S, Matsubara M, Takaoka N, Uemura M, Horiguchi S, Kataoka J, Iwamuro M, Yagi T, Yamamoto K (2011) Restored expression of the tumor suppressor gene RUNX3 reduces cancer stem cells in hepatocellular carcinoma by suppressing Jagged1-Notch signaling. Oncol Rep 26(3):523–531. doi: 10.3892/or.2011.1336 PubMedGoogle Scholar
  101. 101.
    Ouyang M, Li Y, Ye S, Ma J, Lu L, Lv W, Chang G, Li X, Li Q, Wang S, Wang W (2014) MicroRNA profiling implies new markers of chemoresistance of triple-negative breast cancer. PLoS One 9(5):e96228. doi: 10.1371/journal.pone.0096228 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Qin YR, Tang H, Xie F, Liu H, Zhu Y, Ai J, Chen L, Li Y, Kwong DL, Fu L, Guan XY (2011) Characterization of tumor-suppressive function of SOX6 in human esophageal squamous cell carcinoma. Clin Cancer Res 17(1):46–55. doi: 10.1158/1078-0432.CCR-10-1155 PubMedCrossRefGoogle Scholar
  103. 103.
    Pinto R, De Summa S, Pilato B, Tommasi S (2014) DNA methylation and miRNAs regulation in hereditary breast cancer: epigenetic changes, players in transcriptional and post- transcriptional regulation in hereditary breast cancer. Curr Mol Med 14(1):45–57. doi: 10.2174/1566524013666131203101405 PubMedCrossRefGoogle Scholar
  104. 104.
    Lin H, Zhang Y, Wang H, Xu D, Meng X, Shao Y, Lin C, Ye Y, Qian H, Wang S (2012) Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells. Cancer Gene Ther 19(12):845–851. doi: 10.1038/cgt.2012.70 PubMedCrossRefGoogle Scholar
  105. 105.
    Yuan ZY, Dai T, Wang SS, Peng RJ, Li XH, Qin T, Song LB, Wang X (2014) Overexpression of ETV4 protein in triple-negative breast cancer is associated with a higher risk of distant metastasis. Onco Targets Ther 7:1733–1742. doi: 10.2147/OTT.S66692 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Gehrke I, Gandhirajan RK, Kreuzer KA (2009) Targeting the WNT/beta-catenin/TCF/LEF1 axis in solid and haematological cancers: multiplicity of therapeutic options. Eur J Cancer 45(16):2759–2767. doi: 10.1016/j.ejca.2009.08.003 PubMedCrossRefGoogle Scholar
  107. 107.
    Delaunay S, Rapino F, Tharun L, Zhou Z, Heukamp L, Termathe M, Shostak K, Klevernic I, Florin A, Desmecht H, Desmet CJ, Nguyen L, Leidel SA, Willis AE, Büttner R, Chariot A, Close P (2016) Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer. J Exp Med 213(11):2503–2523. doi: 10.1084/jem.20160397 PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Giricz O, Calvo V, Pero SC, Krag DN, Sparano JA, Kenny PA (2012) GRB7 is required for triple-negative breast cancer cell invasion and survival. Breast Cancer Res Treat 33(2):607–615. doi: 10.1007/s10549-011-1822-6 CrossRefGoogle Scholar
  109. 109.
    Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, Griffith M, Moradian A, Cheng SW, Morin GB, Watson P, Gelmon K, Chia S, Chin SF, Curtis C, Rueda OM, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S (2012) The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486(7403):395–399. doi: 10.1038/nature10933 PubMedGoogle Scholar
  110. 110.
    dos Santos PB, Zanetti JS, Ribeiro-Silva A, Beltrão EI (2012) Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study. Diagn Pathol 7:104. doi: 10.1186/1746-1596-7-104 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Mathe A, Wong-Brown M, Locke WJ, Stirzaker C, Braye SG, Forbes JF, Clark SJ, Avery-Kiejda KA, Scott RJ (2016) DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients. Sci Rep 6:33435. doi: 10.1038/srep33435 PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Muñoz M, Coveñas R (2016) Neurokinin-1 receptor antagonists as antitumor drugs in gastrointestinal cancer: a new approach. Saudi J Gastroenterol 22(4):260–268. doi: 10.4103/1319-3767.187601 PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Magnani L, Ballantyne EB, Zhang X, Lupien M (2011) PBX1 genomic pioneer function drives ERα signaling underlying progression in breast cancer. PLoS Genet 7(11):e1002368. doi: 10.1371/journal.pgen.1002368 PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Buas MF, Rho JH, Chai X, Zhang Y, Lampe PD, Li C (2015) Candidate early detection protein biomarkers for ER+/PR+ invasive ductal breast carcinoma identified using pre-clinical plasma from the WHI observational study. Breast Cancer Res Treat 153(2):445–454. doi: 10.1007/s10549-015-3554-5 PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Kulak MV, Cyr AR, Woodfield GW, Bogachek M, Spanheimer PM, Li T, Price DH, Domann FE, Weigel RJ (2013) Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer. Oncogene 32(34):4043–4051. doi: 10.1038/onc.2012.400 PubMedCrossRefGoogle Scholar
  116. 116.
    Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, Telli ML, Advani RH, Carlson RW, Mollick JA, Sheth S, Kurian AW, Ford JM, Stockdale FE, Quake SR, Pease RF, Mindrinos MN, Bhanot G, Dairkee SH, Davis RW, Jeffrey SS (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS One 7(5):e33788. doi: 10.1371/journal.pone.0033788 PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Miyoshi N, Ishii H, Mimori K, Tanaka F, Hitora T, Tei M, Sekimoto M, Doki Y, Mori M (2010) TGM2 is a novel marker for prognosis and therapeutic target in colorectal cancer. Ann Surg Oncol 17(4):967–972. doi: 10.1245/s10434-009-0865-y PubMedCrossRefGoogle Scholar
  118. 118.
    Ai L, Kim WJ, Demircan B, Dyer LM, Bray KJ, Skehan RR, Massoll NA, Brown KD (2008) The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. Carcinogenesis 29(3):510–518. doi: 10.1093/carcin/bgm280 PubMedCrossRefGoogle Scholar
  119. 119.
    Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Investig 121(7):2750–2767. doi: 10.1172/JCI45014 PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    McCullough J, Row PE, Lorenzo O, Doherty M, Beynon R, Clague MJ, Urbé S (2006) Activation of the endosome-associated ubiquitin isopeptidase AMSH by STAM, a component of the multivesicular body-sorting machinery. Curr Biol 16(2):160–165. doi: 10.1016/j.cub.2005.11.073 PubMedCrossRefGoogle Scholar
  121. 121.
    Hinoda Y, Okayama N, Takano N, Fujimura K, Suehiro Y, Hamanaka Y, Hazama S, Kitamura Y, Kamatani N, Oka M (2002) Association of functional polymorphisms of matrix metalloproteinase (MMP)-1 and MMP-3 genes with colorectal cancer. Int J Cancer 102(5):526–529. doi: 10.1002/ijc.10750 PubMedCrossRefGoogle Scholar
  122. 122.
    Han J, Bae SY, Oh SJ, Lee J, Lee JH, Lee HC, Lee SK, Kil WH, Kim SW, Nam SJ, Kim S, Lee JE (2014) Zerumbone suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells. Phytother Res 28(11):1654–1660. doi: 10.1002/ptr.5178 PubMedCrossRefGoogle Scholar
  123. 123.
    An CH, Je EM, Yoo NJ, Lee SH (2015) Frameshift mutations of cadherin genes DCHS2, CDH10 and CDH24 genes in gastric and colorectal cancers with high microsatellite instability. Pathol Oncol Res 21(1):181–185. doi: 10.1007/s12253-014-9804-8 PubMedCrossRefGoogle Scholar
  124. 124.
    Yang C, Zhao X, Cui N, Liang Y (2017) Cadherins associate with distinct stem cell-related transcription factors to coordinate the maintenance of stemness in triple-negative breast cancer. Stem Cells Int 2017:5091541. doi: 10.1155/2017/5091541 PubMedPubMedCentralGoogle Scholar
  125. 125.
    Kresse SH, Ohnstad HO, Paulsen EB, Bjerkehagen B, Szuhai K, Serra M, Schaefer KL, Myklebost O, Meza-Zepeda LA (2009) LSAMP, a novel candidate tumor suppressor gene in human osteosarcomas, identified by array comparative genomic hybridization. Genes Chromosomes Cancer 48(8):679–693. doi: 10.1002/gcc.20675 PubMedCrossRefGoogle Scholar
  126. 126.
    Subramaniam M, Hefferan TE, Tau K, Peus D, Pittelkow M, Jalal S, Riggs BL, Roche P, Spelsberg TC (1998) Tissue, cell type, and breast cancer stage-specific expression of a TGF-beta inducible early transcription factor gene. J Cell Biochem 68(2):226–236PubMedCrossRefGoogle Scholar
  127. 127.
    Iida J, Dorchak J, Clancy R, Slavik J, Ellsworth R, Katagiri Y, Pugacheva EN, van Kuppevelt TH, Mural RJ, Cutler ML, Shriver CD (2015) Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth. Exp Cell Res 330(2):358–370. doi: 10.1016/j.yexcr.2014.11.002 PubMedCrossRefGoogle Scholar
  128. 128.
    Tuna M, Smid M, Zhu D, Martens JW, Amos C (2010) Association between acquired uniparental disomy and homozygous mutations and HER2/ER/PR status in breast cancer. PLoS One 5(11):e15094. doi: 10.1371/journal.pone.0015094 PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Jason BN, Walter CL, Paul AB (2012) Prognosis of treatment response (pathological complete response) in breast cancer. Biomark Insights 7:59–70. doi: 10.4137/BMI.S9387 Google Scholar
  130. 130.
    Hata A, Kashima R (2016) Dysregulation of microRNA biogenesis machinery in cancer. Crit Rev Biochem Mol Biol 51(3):121–134. doi: 10.3109/10409238.2015.1117054 PubMedCrossRefGoogle Scholar
  131. 131.
    Bottai G, Diao L, Baggerly KA, Paladini L, Győrffy B, Raschioni C, Pusztai L, Calin GA, Santarpia L (2017) Integrated microRNA-mRNA profiling identifies oncostatin M as a marker of mesenchymal-like ER-negative/HER2-negative breast cancer. Int J Mol Sci 18(1):E194. doi: 10.3390/ijms18010194 PubMedCrossRefGoogle Scholar
  132. 132.
    Guo X, Cai Q, Bao P, Wu J, Wen W, Ye F, Zheng W, Zheng Y, Shu XO (2016) Long-term soy consumption and tumor tissue MicroRNA and gene expression in triple-negative breast cancer. Cancer 122(16):2544–2551. doi: 10.1002/cncr.29981 PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Berillo O, Régnier M, Ivashchenko A (2013) Binding of intronic miRNAs to the mRNAs of host genes encoding intronic miRNAs and proteins that participate in tumourigenesis. Comput Biol Med 43(10):1374–1381. doi: 10.1016/j.compbiomed.2013.07.011 PubMedCrossRefGoogle Scholar
  134. 134.
    Li J, Li X, Kong X, Luo Q, Zhang J, Fang L (2014) MiRNA-26b inhibits cellular proliferation by targeting CDK8 in breast cancer. Int J Clin Exp Med 7(3):558–565PubMedPubMedCentralGoogle Scholar
  135. 135.
    Lu J, He ML, Wang L, Chen Y, Liu X, Dong Q, Chen YC, Peng Y, Yao KT, Kung HF, Li XP (2011) MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res 71(1):225–233. doi: 10.1158/0008-5472.CAN-10-1850 PubMedCrossRefGoogle Scholar
  136. 136.
    Zhao N, Wang R, Zhou L, Zhu Y, Gong J, Zhuang SM (2014) MicroRNA-26b suppresses the NF-κB signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB 3. Mol Cancer 13:35. doi: 10.1186/1476-4598-13-35 PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Martignetti L, Tesson B, Almeida A, Zinovyev A, Tucker GC, Dubois T, Barillot E (2015) Detection of miRNA regulatory effect on triple negative breast cancer transcriptome. BMC Genom 16:S4. doi: 10.1186/1471-2164-16-S6-S4 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Basavaraj Vastrad
    • 1
  • Chanabasayya Vastrad
    • 2
  • Anandkumar Tengli
    • 3
  • Sudhir Iliger
    • 1
  1. 1.Department of PharmaceuticsSET’s College of PharmacyDharwadIndia
  2. 2.Department of Computer ScienceKarnataka UniversityDharwadIndia
  3. 3.Department of Pharmaceutical Chemistry, JSS College of PharmacyJagadguru Sri Shivarathreeshwara University MysuruMysuruIndia

Personalised recommendations