Epithelial-mesenchymal transition (EMT): Principles and clinical impact in cancer therapy;Transición epitelio-mesenquimática (TEM): Principios e impacto clínico en la terapia contra el cáncer

Investigacion Clinica (Venezuela)

Volumn 54, Issue 2, 2013, Pages 186-205

  Franco Chuaire, María Liliana ^a   Sánchez Corredor, Magda Carolina ^b   Chuaire Noack, Lilian ^b  

^a Escuela de Medicina y Ciencias de la Salud   (Colombia)

^b UNIVERSIDAD DEL ROSARIO   (Colombia)

Author keywords

Cadherins; Cancer; Cancer stem cells; Cell polarity; Differentiation; microRNA

Indexed keywords

BETA CATENIN; FIBROBLAST GROWTH FACTOR; MATRILYSIN; MICRORNA 200; NERVE CELL ADHESION MOLECULE; OSTEOGENIC PROTEIN 1; PROTEIN P120; TRANSCRIPTION FACTOR PAX2; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA; UVOMORULIN; WT1 PROTEIN;

APOPTOSIS; ARTICLE; CANCER THERAPY; CARCINOGENESIS; CELL ADHESION; CELL POLARITY; CELL PROLIFERATION; EMBRYO DEVELOPMENT; EPITHELIAL MESENCHYMAL TRANSITION; FIBROSIS; HUMAN; METASTASIS; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; STEM CELL; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL ADHESION; CELL ADHESION MOLECULES; CELL DIFFERENTIATION; CELL MOVEMENT; CELL POLARITY; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; EMBRYONIC DEVELOPMENT; EPITHELIAL-MESENCHYMAL TRANSITION; FIBROSIS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MICRORNAS; MOLECULAR TARGETED THERAPY; NEOPLASM PROTEINS; NEOPLASMS; NEOPLASTIC STEM CELLS; RNA, NEOPLASM; SIGNAL TRANSDUCTION;

EID: 84878919672     PISSN: 05355133     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (127)

1. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7(2): 131-142.
2. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Investig 2009; 119(6): 1420-1428.
3. Kahn LB, Uys CJ, Dale J, Rutherfoord S. Carcinoma of the breast with metaplasia to chondrosarcoma: a light and electron microscopic study. Histopathology 1978; 2(2): 93-106.
4. Hay ED. An overview of epitheliomesenchymal transformation. Acta Anat (Basel) 1995; 154(1): 8-20.
5. Greenburg G, Hay ED. Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells. J Cell Biol 1982; 95(1): 333-339.
6. Pérez-Pomares JM, Muñoz-Chápuli R. Epithelial-mesenchymal transitions: a mesodermal cell strategy for evolutive innovation in Metazoans. Anat Rec 2002; 268(3): 343-351.
7. Moreno-Bueno G, Portillo F, Cano A. Transcriptional regulation of cell polarity in EMT and cancer. Oncogene 2008; 27(55): 6958-6969.
8. Klymkowsky MW, Savagner P. Epithelial-mesenchymal transition: a cancer researcher's conceptual friend and foe. Am J Pathol 2009; 174(5): 1588-1593.
9. Yang J, Weinberg RA. Epithelialmesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008; 14(6): 818-819.
10. Nieto MA. The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol 2011; 27: 347-376.
11. Davies JA. Mesenchyme to epithelium transition during development of the mammalian kidney tubule. Acta Anat 1996; 156(3): 187-201.
12. Zeisberg M, Shah AA, Kalluri R. Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney. J Biol Chem 2005; 280(9): 8094-8100.
13. Hogan BL, Kolodziej PA. Organogenesis: molecular mechanisms of tubulogenesis. Nat Rev Genet 2002; 3(7): 513-523.
14. Tarin D, Thompson EW, Newgreen DF. The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res 2005; 65(14): 5996-6000.
15. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9(4): 265-273.
16. Ansieau S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, Fauvet F, Puisieux I, Doglioni C, Piccinin S, Maestro R, Voeltzel T, Selmi A, Valsesia-Wittmann S, Caron de Fromentel C, Puisieux A. Induction of EMT by twist proteins as a collateral effect of tumor-pro-moting inactivation of premature senescence. Cancer Cell 2008; 14(1): 79-89.
17. Weinberg RA. Twisted epithelialmesenchymal transition blocks senescence. Nat Cell Biol 2008; 10(9): 1021-1023.
18. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133(4): 704-715.
19. Scheel C, Weinberg RA. Cancer stem cells and epithelial-mesenchymal transition: Concepts and molecular links. Semin Cancer Biol 2012; 22(5-6): 396-403.
20. Fischer AN, Fuchs E, Mikula M, Huber H, Beug H, Mikulits W. PDGF essentially links TGF-beta signaling to nuclear betacatenin accumulation in hepatocellular carcinoma progression. Oncogene 2007; 26(23): 3395-3405.
21. Kim YN, Koo KH, Sung JY, Yun UJ, Kim H. Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol 2012. Doi:101155/2012/306879.
22. Cheng GZ, Chan J, Wang Q, Zhang W, Sun CD, Wang LH. Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion and resistance to paclitaxel. Cancer Res 2007; 67(5): 1979-1987.
23. Emadi Baygi M, Soheili ZS, Essmann F, Deezagi A, Engers R, Goering W, Schulz WA. Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines. Tumour Biol 2010; 31(4): 297-307.
24. Tse JC, Kalluri R. Mechanisms of metastasis: Epithelial-to-Mesenchymal transition and contribution of tumor microenvironment. J Cell Biochem 2007; 101(4): 816-829.
25. Enomoto M, Igaki T. Deciphering tumor-suppressor signaling in flies: Genetic link between Scribble/Dlg/Lgl and the Hippo pathways. J Genet Genomics 2011; 38(10): 461-470.
26. Cavatorta AL, Giri AA, Banks L, Gardiol D. Cloning and functional analysis of the promoter region of the human Disc large gene. Gene 2008; 424(1-2): 87-95.
27. Gaudet S, Langlois MJ, Lue RA, Rivard N, Viel A. The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring. BMC Cell Biol 2011; 12: 55. Doi: 10.1186/1471-2121-12-55.
28. Whiteman EL, Liu CJ, Fearon ER, Margolis B. The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes. Oncogene 2008; 27(27): 3875-3879.
29. Hidalgo-Carcedo C, Hooper S, Chaudhry SI, Williamson P, Harrington K, Leitinger B, Sahai E. Collective cell migration requires suppression of actomyosin at cellcell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nat Cell Biol 2011; 13(1): 49-58.
30. Angst BD, Marcozzi C, Magee AI. The cadherin superfamily: diversity in form and function. J Cell Sci 2001; 114: 629-641.
31. Hudson LG, Zeineldin R, Stack MS. Phenotypic plasticity of neoplastic ovarian epithelium: Unique cadherin profiles in tumor progression. Clin Exp Metastasis 2008; 25(6): 643-655.
32. Hyafil F, Babinet C, Jacob F. Cell-cell interactions in early embryogenesis: a molecular approach to the role of calcium. Cell 1981; 26(3 Pt 1): 447-454.
33. Peyriéras N, Hyafil F, Louvard D, Ploegh HL, Jacob F. Uvomorulin: a nonintegral membrane protein of early mouse embryo. Proc Natl Acad Sci USA 1983; 80(20): 6274-6277.
34. Hatta K, Nose A, Nagafuchi A, Takeichi M. Cloning and expression of cDNA encoding a neural calcium-dependent cell adhesion molecule: its identity in the cadherin gene family. J Cell Biol 1988; 106(3): 873-881.
35. Dericke LDM, Bracke ME. N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signaling. Int J Dev Biol 2004; 48(5-6): 463-476.
36. 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.
37. Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane A, Houen G, Ruco LP, Dejana E. A novel endothelial-specific membrane protein is a marker of cell-cell contacts. J Cell Biol 1992; 118(6): 1511-1522.
38. Hulpiau P, van Roy F. Molecular evolution of the cadherin superfamily. Int J Biochem Cell Biol 2009; 41(2): 349-369.
39. Davis MA, Ireton RC, Reynolds AB. A core function for p120-catenin in cadherin turnover. J Cell Biol 2003; 163(3): 525-534.
40. Klymkowsky MW. Beta-catenin and its regulatory network. Hum Pathol 2005; 36(3): 225-227.
41. Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW. Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol 2007; 213(2): 374-383.
42. Hemavathy K, Ashraf SI, Ip YT. Snail/slug family of repressors slowly going into the fast lane of development and cancer. Gene 2000; 257(1): 1-12.
43. Ciruna B, Rossant J. FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Dev Cell 2001; 1(1): 37-49.
44. Zohn IE, Li Y, Skolnik EY, Anderson KV, Han J, Niswander L. p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell 2006; 125(5): 957-969.
45. Hirano M, Hashimoto S, Yonemura S, Sabe H, Aizawa S. EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelialmesenchymal transition. J Cell Biol 2008; 182(6): 1217-1230.
46. Savagner P, Yamada KM, Thiery JP. The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelialmesenchymal transition. J Cell Biol 1997; 137(6): 1403-1419.
47. Veltmaat JM, Orelio CC, Ward-Van Oostwaard D, Van Rooijen MA, Mummery CL, Defize LH. Snail is an immediate early target gene of parathyroid hormone related peptide signaling in parietal endoderm formation. Int J Dev Biol 2000; 44(3): 297-307.
48. Batlle E, Sancho E, Francí C, Domínguez D, Monfar M, Baulida J, García De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2000; 2(2): 84-89.
49. Guaita S, Puig I, Francí C, Garrido M, Domínguez D, Batlle E, Sancho E, Dedhart S, García de Herreros A, Baulida J. Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. J Biol Chem 2002; 277(42): 39209-39216.
50. Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Höfler H, Becker KF. Differential expression of the epithelialmesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol 2002; 161(5): 1881-1891.
51. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC, Wu KJ. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 2008; 10(3): 295-305.
52. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139(5): 871-890.
53. Hirohashi S. Inactivation of the Ecadherin-mediated cell adhesion system in human cancers. Am J Pathol 1998; 153(2): 333-339.
54. Cheng JC, Chang HM, Leung PC. Egr-1 mediates epidermal growth factor-induced downregulation of E-cadherin expression via Slug in human ovarian cancer cells. Oncogene 2012. doi: 10.1038/onc. 2012.127.
55. Graff JR, Herman JG, Lapidus RG, Chopra H, Xu R, Jarrard DF, Isaacs WB, Pitha PM, Davidson NE, Baylin SB. E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res 1995; 55(22): 5195-5199.
56. Noë V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM, Mareel M. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci 2001; 114(Pt 1): 111-118.
57. Hennig G, Behrens J, Truss M, Frisch S, Reichmann E, Birchmeier W. Progression of carcinoma cells is associated with alterations in chromatin structure and factor binding at the E-cadherin promoter in vivo. Oncogene 1995; 11(3): 475-484.
58. Berx G, van Roy F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol 2009; 1:a003129.
59. Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg RA. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 2010; 12(3): 247-256.
60. Li X, Kong X, Huo Q, Guo H, Yan S, Yuan C, Moran MS, Shao C, Yang Q. Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition. Cancer Sci 2011; 102(6): 1151-1157.
61. Shih W, Yamada S. N-cadherin-mediated cell-cell adhesion promotes cell migration in a three-dimensional matrix. J Cell Sci 2012. doi: 10.1242/jcs.103861.
62. Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR. Cadherin switching. J Cell Sci 2008; 121(Pt 6): 727-735.
63. Radice GL, Rayburn H, Matsunami H, Knudsen KA, Takeichi M, Hynes RO. Developmental defects in mouse embryos lacking N-cadherin. Dev Biol 1997; 181(1):64-78.
64. Maret D, Gruzglin E, Sadr MS, Siu V, Shan W, Koch AW, Seidah NG, Del Maestro RF, Colman DR. Surface expression of precursor N-cadherin promotes tumor cell invasion. Neoplasia 2010; 12(12): 1066-1080.
65. Ko KS, Arora PD, McCulloch CA. Cadherins mediate intercellular mechanical signaling in fibroblasts by activation of stretch-sensitive calcium-permeable channels. J Biol Chem 2001; 276(38): 35967-35977.
66. Theisen CS, Wahl III JK, Johnson KR, Wheelock MJ. NHERF links the Ncadherin/ catenin complex to the plateletderived growth factor receptor to modulate the actin cytoskeleton and regulate cell motility. Mol Biol Cell 2007; 18(4): 1220-1232.
67. Nieman MT, Prudoff RS, Johnson KR, Wheelock MJ. N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 1999; 147(3): 631-644.
68. 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.
69. Tomita K, van Bokhoven A, van Leenders GJ, Ruijter ET, Jansen CF, Bussemakers MJ, Schalken JA. Cadherin switching in human prostate cancer progression. Cancer Res 2000; 60(13): 3650-3654.
70. ElMoneim HM, Zaghloul NM. Expression of E-cadherin, N-cadherin and snail and their correlation with clinicopathological variants: an immunohistochemical study of 132 invasive ductal breast carcinomas in Egypt. Clinics (Sao Paulo) 2011; 66(10):1 765-1771.
71. Cadigan KM. TCFs and Wnt/T-catenin signaling: more than one way to throw the switch. Curr Top Dev Biol 2012; 98: 1-34.
72. Liu X, Rubin JS, Kimmel AR. Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by G alpha proteins. Curr Biol 2005; 15(22): 1989-1997.
73. Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. Functional interaction of F-catenin with the transcription factor LEF-1. Nature 1996; 382: 638-642.
74. Vallin J, Thuret R, Giacomello E, Faraldo MM, Thiery JP, Broders F. Cloning and characterization of three Xenopus slug promoters reveal direct regulation by Lef/ beta-catenin signaling. J Biol Chem 2001; 276(32): 30350-30358.
75. Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev 2007; 17(1): 45-51.
76. Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG, Kemler R. Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev 1996; 59(1): 3-10.
77. Reynolds AB. p120-catenin: Past and present. Biochim Biophys Acta 2007; 1773(1): 2-7.
78. Zhu YT, Chen HC, Chen SY, Tseng SC. Nuclear p120-catenin unlocks mitotic block of contact-inhibited human corneal endothelial monolayers without disrupting adherent junction. J Cell Sci 2012 doi: 10.1242/jcs.103267.
79. Liu H, Jiang D, Chi F, Zhao B. The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation. Protein Cell 2012; 3(4): 291-304.
80. Jiang G, Wang Y, Dai S, Liu Y, Stoecker M, Wang E, Wang E. P120-catenin isoforms 1 and 3 regulate proliferation and cell cycle of lung cancer cells via c-catenin and Kaiso respectively. PLoS One 2012; 7(1): e30303.
81. Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA. The transcription factor snail controls epithelialmesenchymal transitions by repressing Ecadherin expression. Nat Cell Biol 2000; 2(2): 76-83.
82. Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol 2002; 3(3):155-166.
83. Bolós V, Peinado H, Pérez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci 2003; 116(Pt 3): 499-511.
84. Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007; 7(6): 415-428.
85. Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia 2010; 15(2): 117-134.
86. Zavadil J, Cermak L, Soto-Nieves N, Bottinger EP. Integration of TGF-beta/ Smad and Jagged1/ Notch signalling in epithelial-to-mesenchymal transition. EMBO J 2004; 23(5): 1155-1165.
87. Niessen K, Fu Y, Chang L, Hoodless PA, McFadden D, Karsan A. Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J Cell Biol 2008; 182(2): 315-325.
88. Wang Z, Li Y, Kong D, Sarkar FH. The role of notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Curr Drug Targets 2010; 11(6): 745-751.
89. Jiang J, Tang YL, Liang XH. EMT: a new vision of hypoxia promoting cancer progression. Cancer Biol Ther 2011; 11(8): 714-723.
90. Stepniak E, Radice GL, Vasioukhin V. Adhesive and signaling functions of cadherins and catenins in vertebrate development. Cold Spring Harb Perspect Biol 2009; 1(5): a002949.
91. Spaderna S, Schmalhofer O, Wahlbuhl M, Dimmler A, Bauer K, Sultan A, Hlubek F, Jung A, Strand D, Eger A, Kirchner T, Behrens J, Brabletz T. The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res 2008; 68(2): 537-544.
92. Wang X, Nie J, Zhou Q, Liu W, Zhu F, Chen W, Mao H, Luo N, Dong X, Yu X. Downregulation of Par-3 expression and disruption of Par complex integrity by TGF-beta during the process of epithelial to mesenchymal transition in rat proximal epithelial cells. Biochim Biophys Acta 2008; 1782(1): 51-59.
93. Strippoli R, Benedicto I, Lozano MLP, Cerezo A, López-Cabrera M, Del Pozo MA. Epithelial-to-mesenchymal transition of peritoneal mesothelial cells is regulated by an ERK/NF-bb/Snail1 pathway. Dis Model Mech 2008; 1(4-5): 264-274.
94. Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001; 29(2): 117-129.
95. Tang B, Vu M, Booker T, Santner SJ, Miller FR, Anver MR, Wakefield LM. TGF-TTswitches from tumor suppressor to prometastatic factor in a model of breast cancer progression. J Clin Invest 2003; 112(7): 1116-1124.
96. Larue L, Bellacosa A. Epithelialmesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene 2005; 24(50): 7443-7454.
97. Huang S, Chen LY, Zuraw BL, Ye RD, Pan ZK. Chemoattractant-stimulated NF-kappaC activation is dependent on the low molecular weight GTPaseRhoA. J Biol Chem 2001; 276(44): 40977-40981.
98. Huang S, Pettaway CA, Uehara H, Bucana CD, Fidler IJ. Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene 2001; 20(31): 4188-4197.
99. Bhowmick NA, Ghiassi M, Bakin A, Aakre M, Lundquist CA, Engel ME, Arteaga CL, Moses HL. Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell 2001; 12(1): 27-36.
100. Chen D, Zhang Y, Zhang X, Li J, Han B, Liu S, Wang L, Ling Y, Mao S, Wang X. Overexpression of integrin-linked kinase correlates with malignant phenotype in non-small cell lung cancer and promotes lung cancer cell invasion and migration via regulating epithelial-mesenchymal transition (EMT)-related genes. Acta Histochem 2013; 115(2): 128-136.
101. Tomlinson DC, Baxter EW, Loadman PM, Hull MA, Knowles MA. FGFR1-Induced Epithelial to Mesenchymal Transition through MAPK/PLCM/COX-2-Mediated Mechanisms. PLoS One 2012; 7(6): e38972.
102. Boudreau HE, Casterline BW, Rada B, Korzeniowska A, Leto TL. Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells. Free Radic Biol Med 2012; 53(7): 1489-1499.
103. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007; 449(7162): 557-563.
104. Soria G, Ofri-Shahak M, Haas I, Yaal-Hahoshen N, Leider-Trejo L, Leibovich-Rivkin T, Weitzenfeld P, Meshel T, Shabtai E, Gutman M, Ben-Baruch A. Inflammatory mediators in breast cancer: coordinated expression of TNFee& IL-1&&with CCL2 & CCL5 and effects on epithelial-tomesenchymal transition. BMC Cancer 2011; 11: 130.
105. Bonde AK, Tischler V, Kumar S, Soltermann A, Schwendener RA. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors. BMC Cancer 2012; 12: 35.
106. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-674.
107. Al-Hajj M, Wicha MS, Benito-Hernández A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-3988.
108. Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 2003; 100(25):15178-15183.
109. Lin RY. New insights into thyroid stem cells. Thyroid 2007; 17(10): 1019-1023.
110. Lawson DA, Witte ON. Stem cells in prostate cancer initiation and progression. J Clin Invest 2007; 117(8): 2044-2050.
111. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007; 104(3): 973-978.
112. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3(7): 730-737.
113. Zhang Y, Toy KA, Kleer CG. Metaplastic breast carcinomas are enriched in markers of tumor-initiating cells and epithelial to mesenchymal transition. Mod Pathol 2012; 25(2): 178-184.
114. Diaz-Cano SJ. Tumor Heterogeneity: Mechanisms and bases for a reliable application of molecular marker design. Int J Mol Sci 2012; 13: 1951-2011.
115. Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC. Expression of microRNA-146 suppresses NF-kappammactivity with reduction of metastatic potential in breast cancer cells. Oncogene 2008; 27(42): 5643-5647.
116. Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR. Breast cancer metastasis suppressor 1 BRMS1 up-regulates miR-146 that suppresses breast cancer metastasis. Cancer Res 2009; 69(4): 1279-1283.
117. Hurst DR, Edmonds MD, Welch DR. Metastamir-the field of metastasis-regulatory microRNA is spreading. Cancer Res 2009; 69(19): 7495-7498.
118. Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle 2009; 8(6): 843-852.
119. 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.
120. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celià-Terrassa T, Mercatali L, Khan Z, Goodarzi H, Hua Y, Wei Y, Hu G, García BA, Ragoussis J, Amadori D, Harris AL, Kang Y. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med 2011; 17(9): 1101-1108.
121. Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, Enzo E, Guzzardo V, Rondina M, Spruce T, Parenti AR, Daidone MG, Bicciato S, Piccolo S. A MicroRNA targeting dicer for metastasis control. Cell 2010; 141(7): 1195-1207.
122. Zhang J, Ma L. MicroRNA control of epithelial-mesenchymal transition and metastasis. Cancer Metastasis Rev 2012; 31(3-4): 653-662.
123. Singh B, Tai K, Madan S, Raythatha MR, Cady AM, Braunlin M, Irving LR, Bajaj A, Lucci A. Selection of metastatic breast cancer cells based on adaptability of their metabolic state. PLoS One 2012; 7(5): e36510.
124. Shackleton M. Moving targets that drive cancer progression N Engl J Med 2010; 363(9): 885-886.
125. Lönn P, Van der Heide LP, Dahl M, Hellman U, Heldin CH, Moustakas A. PARP-1 attenuates Smad-mediated transcription. Mol Cell 2010; 40(4): 521-532.
126. Rodríguez MI, González-Flores A, Dantzer F, Collard J, de Herreros AG, Oliver FJ. Poly(ADP-ribose)-dependent regulation of Snail1 protein stability. Oncogene 2011; 30(42): 4365-4372.
127. Olmeda D, Jorda M, Peinado H, Fabra A, Cano A. Snail silencing effectively suppresses tumour growth and invasiveness. Oncogene 2007; 26(13): 1862-1874.