Gene expression analyses of primary melanomas reveal CTHRC1 as an important player in melanoma progression

Oncotarget

Volumn 7, Issue 12, 2016, Pages 15065-15092

  Eriksson, Johanna ^a   Le Joncour, Vadim ^a   Nummela, Pirjo ^a   Jahkola, Tiina ^b   Virolainen, Susanna ^a   Laakkonen, Pirjo ^a   Saksela, Olli ^b   Hölttä, Erkki ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

^b HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

Author keywords

CTHRC1; Invasion metastasis; Melanoma; NFATC2; TGF

Indexed keywords

B RAF KINASE; BETA3 INTEGRIN; FIBRONECTIN; MESSENGER RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NFATC2; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; CTHRC1 PROTEIN, HUMAN; FN1 PROTEIN, HUMAN; ITGB3 PROTEIN, HUMAN; NFATC2 PROTEIN, HUMAN; SCLEROPROTEIN; TRANSCRIPTION FACTOR NFAT; TUMOR MARKER;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER GROWTH; CONTROLLED STUDY; CTHRC1 GENE; DOWN REGULATION; FEMALE; GENE EXPRESSION PROFILING; GENE IDENTIFICATION; GENETIC ASSOCIATION; HUMAN; HUMAN CELL; HUMAN TISSUE; MAJOR CLINICAL STUDY; MELANOMA; METASTATIC MELANOMA; MOUSE; NONHUMAN; PRIMARY TUMOR; TUMOR GENE; UPREGULATION; ANIMAL; APOPTOSIS; BAGG ALBINO MOUSE; CANCER STAGING; CELL ADHESION; CELL MOTION; CELL PROLIFERATION; DISEASE EXACERBATION; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; MELANOCYTE; METABOLISM; NUDE MOUSE; PATHOLOGY; PROGNOSIS; SKIN TUMOR; STROMA CELL; TUMOR CELL CULTURE;

ANIMALS; APOPTOSIS; BIOMARKERS, TUMOR; CELL ADHESION; CELL MOVEMENT; CELL PROLIFERATION; DISEASE PROGRESSION; EXTRACELLULAR MATRIX PROTEINS; FEMALE; FIBRONECTINS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTEGRIN BETA3; MELANOCYTES; MELANOMA; MICE; MICE, INBRED BALB C; MICE, NUDE; NEOPLASM STAGING; NFATC TRANSCRIPTION FACTORS; PROGNOSIS; SKIN NEOPLASMS; STROMAL CELLS; TUMOR CELLS, CULTURED; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84962840617     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.7604     Document Type: Article

References (96)

1. Villanueva J, Herlyn M. Melanoma. In: Encyclopedia of Life Sciences (ELS). John Wiley & Sons, Ltd, Chichester. 2009.
2. Flaherty KT, Hodi FS, Fisher DE. From genes to drugs: targeted strategies for melanoma. Nat Rev Cancer. 2012; 12: 349-361.
3. Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R. TERT promoter mutations in familial and sporadic melanoma. Science. 2013; 339: 959-961.
4. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science. 2013; 339: 957-959.
5. Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg. 1970; 172: 902-908.
6. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009; 27: 6199-6206.
7. Murali R, Haydu LE, Quinn MJ, Saw RP, Shannon K, Spillane AJ, Stretch JR, Thompson JF, Scolyer RA. Sentinel lymph node biopsy in patients with thin primary cutaneous melanoma. Ann Surg. 2012; 255: 128-133.
8. van Akkooi AC, Verhoef C, Eggermont AM. Importance of tumor load in the sentinel node in melanoma: clinical dilemmas. Nat Rev Clin Oncol. 2010; 7: 446-454.
9. Eggermont AM, Spatz A, Robert C. Cutaneous melanoma. Lancet. 2014; 383: 816-827.
10. Mustafa D, van der Weiden M, Zheng P, Nigg A, Luider TM, Kros JM. Expression sites of colligin 2 in glioma blood vessels. Brain Pathol. 2010; 20: 50-65.
11. Astorgues-Xerri L, Riveiro ME, Tijeras-Raballand A, Serova M, Neuzillet C, Albert S, Raymond E, Faivre S. Unraveling galectin-1 as a novel therapeutic target for cancer. Cancer Treat Rev. 2014; 40: 307-319.
12. Hur K, Han TS, Jung EJ, Yu J, Lee HJ, Kim WH, Goel A, Yang HK. Up-regulated expression of sulfatases (SULF1 and SULF2) as prognostic and metastasis predictive markers in human gastric cancer. J Pathol. 2012; 228: 88-98.
13. Chen SY, Lin JS, Yang BC. Modulation of tumor cell stiffness and migration by type IV collagen through direct activation of integrin signaling pathway. Arch Biochem Biophys. 2014; 555-556: 1-8.
14. Schubert K, Gutknecht D, Koberle M, Anderegg U, Saalbach A. Melanoma cells use Thy-1 (CD90) on endothelial cells for metastasis formation. Am J Pathol. 2013; 182: 266-276.
15. Lee KW, Sung CO, Kim JH, Kang M, Yoo HY, Kim HH, Um SH, Kim SH. CD10 expression is enhanced by Twist1 and associated with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro and in vivo. Int J Cancer. 2015; 136: 310-321.
16. Canesin G, Cuevas EP, Santos V, Lopez-Menendez C, Moreno-Bueno G, Huang Y, Csiszar K, Portillo F, Peinado H, Lyden D, Cano A. Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization. Oncogene. 2014; 34: 951-964.
17. Nyren-Erickson EK, Jones JM, Srivastava DK, Mallik S. A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications. Biochim Biophys Acta. 2013; 1830: 4445-4455.
18. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 2010; 29: 625-634.
19. Gilkes DM, Semenza GL, Wirtz D. Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer. 2014; 14: 430-439.
20. Pyagay P, Heroult M, Wang Q, Lehnert W, Belden J, Liaw L, Friesel RE, Lindner V. Collagen triple helix repeat containing 1, a novel secreted protein in injured and diseased arteries, inhibits collagen expression and promotes cell migration. Circ Res. 2005; 96: 261-268.
21. Park EH, Kim S, Jo JY, Kim SJ, Hwang Y, Kim JM, Song SY, Lee DK, Koh SS. Collagen triple helix repeat containing-1 promotes pancreatic cancer progression by regulating migration and adhesion of tumor cells. Carcinogenesis. 2013; 34: 694-702.
22. Perotti V, Baldassari P, Bersani I, Molla A, Vegetti C, Tassi E, Dal Col J, Dolcetti R, Anichini A, Mortarini R. NFATc2 is a potential therapeutic target in human melanoma. J Invest Dermatol. 2012; 132: 2652-2660.
23. LeClair RJ, Durmus T, Wang Q, Pyagay P, Terzic A, Lindner V. Cthrc1 is a novel inhibitor of transforming growth factor-beta signaling and neointimal lesion formation. Circ Res. 2007; 100: 826-833.
24. Flockhart RJ, Armstrong JL, Reynolds NJ, Lovat PE. NFAT signalling is a novel target of oncogenic BRAF in metastatic melanoma. Br J Cancer. 2009; 101: 1448-1455.
25. Miller VL, Lin HK, Murugan P, Fan M, Penning TM, Brame LS, Yang Q, Fung KM. Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma. Int J Clin Exp Pathol. 2012; 5: 278-289.
26. Tian Y, Zhao L, Zhang H, Liu X, Zhao L, Zhao X, Li Y, Li J. AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression. Diagn Pathol. 2014; 9: 42.
27. Mantel A, Carpenter-Mendini A, VanBuskirk J, Pentland AP. Aldo-keto Reductase 1C3 (AKR1C3) is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism. Exp Dermatol. 2014; 23: 573-578.
28. Wu CH, Ko JL, Chen SC, Lin YW, Han CP, Yang TY, Chien MH, Wang PH. Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix. Gynecol Oncol. 2014; 132: 474-482.
29. De Rosa A, Pellegatta S, Rossi M, Tunici P, Magnoni L, Speranza MC, Malusa F, Miragliotta V, Mori E, Finocchiaro G, Bakker A. A radial glia gene marker, fatty acid binding protein 7 (FABP7), is involved in proliferation and invasion of glioblastoma cells. PLoS One. 2012; 7: e52113.
30. Mita R, Beaulieu MJ, Field C, Godbout R. Brain fatty acid-binding protein and omega-3/omega-6 fatty acids: mechanistic insight into malignant glioma cell migration. J Biol Chem. 2010; 285: 37005-37015.
31. Bravo-Cordero JJ, Magalhaes MA, Eddy RJ, Hodgson L, Condeelis J. Functions of cofilin in cell locomotion and invasion. Nat Rev Mol Cell Biol. 2013; 14: 405-415.
32. Weide B, Richter S, Buttner P, Leiter U, Forschner A, Bauer J, Held L, Eigentler TK, Meier F, Garbe C. Serum S100B, lactate dehydrogenase and brain metastasis are prognostic factors in patients with distant melanoma metastasis and systemic therapy. PLoS One. 2013; 8: e81624.
33. Kruijff S, Hoekstra HJ. The current status of S-100B as a biomarker in melanoma. Eur J Surg Oncol. 2012; 38: 281-285.
34. Kääriäinen E, Nummela P, Soikkeli J, Yin M, Lukk M, Jahkola T, Virolainen S, Ora A, Ukkonen E, Saksela O, Hölttä E. Switch to an invasive growth phase in melanoma is associated with tenascin-C, fibronectin, and procollagen-I forming specific channel structures for invasion. J Pathol. 2006; 210: 181-191.
35. Soikkeli J, Podlasz P, Yin M, Nummela P, Jahkola T, Virolainen S, Krogerus L, Heikkilä P, von Smitten K, Saksela O, Hölttä E. Metastatic outgrowth encompasses COL-I, FN1, and POSTN up-regulation and assembly to fibrillar networks regulating cell adhesion, migration, and growth. Am J Pathol. 2010; 177: 387-403.
36. Gilkes DM, Chaturvedi P, Bajpai S, Wong CC, Wei H, Pitcairn S, Hubbi ME, Wirtz D, Semenza GL. Collagen prolyl hydroxylases are essential for breast cancer metastasis. Cancer Res. 2013; 73: 3285-3296.
37. Gebhardt C, Nemeth J, Angel P, Hess J. S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol. 2006; 72: 1622-1631.
38. Scala S, Ottaiano A, Ascierto PA, Cavalli M, Simeone E, Giuliano P, Napolitano M, Franco R, Botti G, Castello G. Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma. Clin Cancer Res. 2005; 11: 1835-1841.
39. Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res. 2010; 16: 2927-2931.
40. Jiang L, Lv X, Li J, Li J, Li X, Li W, Li Y. The status of microRNA-21 expression and its clinical significance in human cutaneous malignant melanoma. Acta Histochem. 2012; 114: 582-588.
41. Song T, Dou C, Jia Y, Tu K, Zheng X. TIMP-1 activated carcinoma-associated fibroblasts inhibit tumor apoptosis by activating SDF1/CXCR4 signaling in hepatocellular carcinoma. Oncotarget. 2015; 6: 12061-12079. doi: 10.18632/oncotarget.3616.
42. Cui H, Seubert B, Stahl E, Dietz H, Reuning U, Moreno-Leon L, Ilie M, Hofman P, Nagase H, Mari B, Kruger A. Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes. Oncogene. 2015; 34:3640-50. doi: 10.1038/onc.2014.300.
43. Wang K, Wang B, Xing AY, Xu KS, Li GX, Yu ZH. Prognostic significance of SERPINE2 in gastric cancer and its biological function in SGC7901 cells. J Cancer Res Clin Oncol. 2015; 141: 805-812.
44. Wagenblast E, Soto M, Gutierrez-Angel S, Hartl CA, Gable AL, Maceli AR, Erard N, Williams AM, Kim SY, Dickopf S, Harrell JC, Smith AD, Perou CM, et al. A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Nature. 2015; 520: 358-362.
45. Cheon DJ, Tong Y, Sim MS, Dering J, Berel D, Cui X, Lester J, Beach JA, Tighiouart M, Walts AE, Karlan BY, Orsulic S. A collagen-remodeling gene signature regulated by TGF-beta signaling is associated with metastasis and poor survival in serous ovarian cancer. Clin Cancer Res. 2014; 20: 711-723.
46. Soikkeli J, Lukk M, Nummela P, Virolainen S, Jahkola T, Katainen R, Harju L, Ukkonen E, Saksela O, Hölttä E. Systematic search for the best gene expression markers for melanoma micrometastasis detection. J Pathol. 2007; 213: 180-189.
47. Ignotz RA, Endo T, Massague J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J Biol Chem. 1987; 262: 6443-6446.
48. Fernandez-Zapico ME, Ellenrieder V. NFAT transcription factors, the potion mediating 'Dr. Jekill-Mr. Hyde' trans- formation of the TGFbeta pathway in cancer cells. Cell Cycle. 2010; 9: 3838-3839.
49. Platten M, Wick W, Wild-Bode C, Aulwurm S, Dichgans J, Weller M. Transforming growth factors beta(1) (TGF-beta(1)) and TGF-beta(2) promote glioma cell migration via Up-regulation of alpha(V)beta(3) integrin expression. Biochem Biophys Res Commun. 2000; 268: 607-611.
50. Faralli JA, Gagen D, Filla MS, Crotti TN, Peters DM. Dexamethasone increases alphavbeta3 integrin expression and affinity through a calcineurin/NFAT pathway. Biochim Biophys Acta. 2013; 1833: 3306-3313.
51. Albelda SM, Mette SA, Elder DE, Stewart R, Damjanovich L, Herlyn M, Buck CA. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 1990; 50: 6757-6764.
52. Hsu MY, Shih DT, Meier FE, Van Belle P, Hsu JY, Elder DE, Buck CA, Herlyn M. Adenoviral gene transfer of beta3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma. Am J Pathol. 1998; 153: 1435-1442.
53. Ross FP, Chappel J, Alvarez JI, Sander D, Butler WT, Farach-Carson MC, Mintz KA, Robey PG, Teitelbaum SL, Cheresh DA. Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption. J Biol Chem. 1993; 268: 9901-9907.
54. Lawler J, Weinstein R, Hynes RO. Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors. J Cell Biol. 1988; 107: 2351-2361.
55. Charo IF, Nannizzi L, Smith JW, Cheresh DA. The vitronectin receptor alpha v beta 3 binds fibronectin and acts in concert with alpha 5 beta 1 in promoting cellular attachment and spreading on fibronectin. J Cell Biol. 1990; 111: 2795-2800.
56. Yin M, Soikkeli J, Jahkola T, Virolainen S, Saksela O, Hölttä E. Osteopontin promotes the invasive growth of melanoma cells by activating integrin alphavbeta3 and down-regulating tetraspanin CD9. Am J Pathol. 2014; 184: 842-858.
57. Tanabe N, Wheal BD, Kwon J, Chen HH, Shugg RP, Sims SM, Goldberg HA, Dixon SJ. Osteopontin signals through calcium and nuclear factor of activated T cells (NFAT) in osteoclasts: a novel RGD-dependent pathway promoting cell survival. J Biol Chem. 2011; 286: 39871-39881.
58. Wang P, Wang YC, Chen XY, Shen ZY, Cao H, Zhang YJ, Yu J, Zhu JD, Lu YY, Fang JY. CTHRC1 is upregulated by promoter demethylation and transforming growth factor-beta1 and may be associated with metastasis in human gastric cancer. Cancer Sci. 2012; 103: 1327-1333.
59. Chen YL, Wang TH, Hsu HC, Yuan RH, Jeng YM. Overexpression of CTHRC1 in hepatocellular carcinoma promotes tumor invasion and predicts poor prognosis. PLoS One. 2013; 8: e70324.
60. Kharaishvili G, Cizkova M, Bouchalova K, Mgebrishvili G, Kolar Z, Bouchal J. Collagen triple helix repeat containing 1 protein, periostin and versican in primary and metastatic breast cancer: an immunohistochemical study. J Clin Pathol. 2011; 64: 977-982.
61. Ke Z, He W, Lai Y, Guo X, Chen S, Li S, Wang Y, Wang L. Overexpression of collagen triple helix repeat containing 1 (CTHRC1) is associated with tumour aggressiveness and poor prognosis in human non-small cell lung cancer. Oncotarget. 2014; 5: 9410-9424. doi: 10.18632/oncotarget.2421.
62. Tang L, Dai DL, Su M, Martinka M, Li G, Zhou Y. Aberrant expression of collagen triple helix repeat containing 1 in human solid cancers. Clin Cancer Res. 2006; 12: 3716-3722.
63. Kim JH, Baek TH, Yim HS, Kim KH, Jeong SH, Kang HB, Oh SS, Lee HG, Kim JW, Kim KD. Collagen triple helix repeat containing-1 (CTHRC1) expression in invasive ductal carcinoma of the breast: the impact on prognosis and correlation to clinicopathologic features. Pathol Oncol Res. 2013; 19: 731-737.
64. Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers WR, Polyak K. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell. 2004; 6: 17-32.
65. West RB, Nuyten DS, Subramanian S, Nielsen TO, Corless CL, Rubin BP, Montgomery K, Zhu S, Patel R, Hernandez-Boussard T, Goldblum JR, Brown PO, van de Vijver M, et al. Determination of stromal signatures in breast carcinoma. PLoS Biol. 2005; 3: e187.
66. Yin M, Soikkeli J, Jahkola T, Virolainen S, Saksela O, Holtta E. TGF-beta signaling, activated stromal fibroblasts, and cysteine cathepsins B and L drive the invasive growth of human melanoma cells. Am J Pathol. 2012; 181: 2202-2216.
67. Mahabeleshwar GH, Feng W, Phillips DR, Byzova TV. Integrin signaling is critical for pathological angiogenesis. J Exp Med. 2006; 203: 2495-2507.
68. Mahabeleshwar GH, Feng W, Reddy K, Plow EF, Byzova TV. Mechanisms of integrin-vascular endothelial growth factor receptor cross-activation in angiogenesis. Circ Res. 2007; 101: 570-580.
69. Hernandez GL, Volpert OV, Iniguez MA, Lorenzo E, Martinez-Martinez S, Grau R, Fresno M, Redondo JM. Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med. 2001; 193: 607-620.
70. Astrof S, Hynes RO. Fibronectins in vascular morpho- genesis. Angiogenesis. 2009; 12: 165-175.
71. Rybak JN, Roesli C, Kaspar M, Villa A, Neri D. The extra-domain A of fibronectin is a vascular marker of solid tumors and metastases. Cancer Res. 2007; 67: 10948-10957.
72. Castellani P, Viale G, Dorcaratto A, Nicolo G, Kaczmarek J, Querze G, Zardi L. The fibronectin isoform containing the ED-B oncofetal domain: a marker of angiogenesis. Int J Cancer. 1994; 59: 612-618.
73. Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res. 2006; 312: 584-593.
74. Glinka Y, Stoilova S, Mohammed N, Prud'homme GJ. Neuropilin-1 exerts co-receptor function for TGF-beta-1 on the membrane of cancer cells and enhances responses to both latent and active TGF-beta. Carcinogenesis. 2011; 32: 613-621.
75. Stine MJ, Wang CJ, Moriarty WF, Ryu B, Cheong R, Westra WH, Levchenko A, Alani RM. Integration of genotypic and phenotypic screening reveals molecular mediators of melanoma-stromal interaction. Cancer Res. 2011; 71: 2433-2444.
76. Yamamoto S, Nishimura O, Misaki K, Nishita M, Minami Y, Yonemura S, Tarui H, Sasaki H. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008; 15: 23-36.
77. Jonsson M, Smith K, Harris AL. Regulation of Wnt5a expression in human mammary cells by protein kinase C activity and the cytoskeleton. Br J Cancer. 1998; 78: 430-438.
78. Saneyoshi T, Kume S, Amasaki Y, Mikoshiba K. The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature. 2002; 417: 295-299.
79. Griesmann H, Ripka S, Pralle M, Ellenrieder V, Baumgart S, Buchholz M, Pilarsky C, Aust D, Gress TM, Michl P. WNT5A-NFAT signaling mediates resistance to apoptosis in pancreatic cancer. Neoplasia. 2013; 15: 11-22.
80. Wang Y, Shibasaki F, Mizuno K. Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin. J Biol Chem. 2005; 280: 12683-12689.
81. Matus DQ, Lohmer LL, Kelley LC, Schindler AJ, Kohrman AQ, Barkoulas M, Zhang W, Chi Q, Sherwood DR. Invasive Cell Fate Requires G1 Cell-Cycle Arrest and Histone Deacetylase-Mediated Changes in Gene Expression. Dev Cell. 2015; 35: 162-174.
82. Gil-Henn H, Patsialou A, Wang Y, Warren MS, Condeelis JS, Koleske AJ. Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo. Oncogene. 2013; 32: 2622-2630.
83. Hou M, Cheng Z, Shen H, He S, Li Y, Pan Y, Feng C, Chen X, Zhang Y, Lin M, Wang L, Ke Z. High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis. Oncotarget. 2015; 6: 35813-35829. doi: 10.18632/oncotarget.5358.
84. Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DV, Byrom D, Cortina C, Morral C, Barcelo C, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015; 47: 320-329.
85. Miles FL, Sikes RA. Insidious changes in stromal matrix fuel cancer progression. Mol Cancer Res. 2014; 12: 297-312.
86. Liu JF, Zhao SH, Wu SS. Depleting NFAT1 expression inhibits the ability of invasion and migration of human lung cancer cells. Cancer Cell Int. 2013; 13: 41.
87. Mancini M, Toker A. NFAT proteins: emerging roles in cancer progression. Nat Rev Cancer. 2009; 9: 810-820.
88. Medyouf H, Ghysdael J. The calcineurin/NFAT signaling pathway: a novel therapeutic target in leukemia and solid tumors. Cell Cycle. 2008; 7: 297-303.
89. Pickup M, Novitskiy S, Moses HL. The roles of TGFbeta in the tumour microenvironment. Nat Rev Cancer. 2013; 13: 788-799.
90. Singh G, Singh SK, Konig A, Reutlinger K, Nye MD, Adhikary T, Eilers M, Gress TM, Fernandez-Zapico ME, Ellenrieder V. Sequential activation of NFAT and c-Myc transcription factors mediates the TGF-beta switch from a suppressor to a promoter of cancer cell proliferation. J Biol Chem. 2010; 285: 27241-27250.
91. Sengupta S, Jana S, Biswas S, Mandal PK, Bhattacharyya A. Cooperative involvement of NFAT and SnoN mediates transforming growth factor-beta (TGF-beta) induced EMT in metastatic breast cancer (MDA-MB 231) cells. Clin Exp Metastasis. 2013; 30: 1019-1031.
92. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001; 98: 5116-5121.
93. Kielosto M, Nummela P, Katainen R, Leaner V, Birrer MJ, Hölttä E. Reversible regulation of the transformed phenotype of ornithine decarboxylase- and ras-overex- pressing cells by dominant-negative mutants of c-Jun. Cancer Res. 2004; 64: 3772-3779.
94. Ravanko K, Järvinen K, Helin J, Kalkkinen N, Hölttä E. Cysteine cathepsins are central contributors of invasion by cultured adenosylmethionine decarboxylase-transformed rodent fibroblasts. Cancer Res. 2004; 64: 8831-8838.
95. Nummela P, Lammi J, Soikkeli J, Saksela O, Laakkonen P, Hölttä E. Transforming growth factor beta-induced (TGFBI) is an anti-adhesive protein regulating the invasive growth of melanoma cells. Am J Pathol. 2012; 180: 1663-1674.
96. Alanko T, Rosenberg M, Saksela O. FGF expression allows nevus cells to survive in three-dimensional collagen gel under conditions that induce apoptosis in normal human melanocytes. J Invest Dermatol. 1999; 113: 111-116.