• 1
    Klymkowsky MW and Savagner P. Epithelial-mesenchymal transition: a cancer researcher's conceptual friend and foe. American Journal of Pathology 2009; 174: 15881593.
  • 2
    Shook D and Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mechanisms of Development 2003; 120: 13511383.
  • 3
    Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Current Opinion in Cell Biology 2003; 15: 740746.
  • 4
    Acloque H, Adams MS, Fishwick K, Bronner-Fraser M and Nieto MA. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. The Journal of Clinical Investigation 2009; 119: 14381449.
  • 5
    Savagner P, Boyer B, Valles AM, Jouanneau J and Thiery JP. Modulations of the epithelial phenotype during embryogenesis and cancer progression. Cancer Treatment and Research 1994; 71: 229249.
  • 6
    Thiery JP and Chopin D. Epithelial cell plasticity in development and tumor progression. Cancer Metastasis Reviews 1999; 18: 3142.
  • 7
    Kalluri R and Weinberg RA. The basics of epithelial-mesenchymal transition. The Journal of Clinical Investigation 2009; 119: 14201428.
  • 8
    De Wever O, Pauwels P, De Craene B, Sabbah M, Emami S, Redeuilh G, Gespach C, Bracke M and Berx G. Molecular and pathological signatures of epithelial-mesenchymal transition at the cancer invasion front. Histochemistry and Cell Biology 2008; 130: 481494.
  • 9
    Voulgari A and Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochimica et Biophysica Acta 2009; 1796: 7590.
  • 10
    Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nature Reviews Cancer 2002; 2: 442454.
  • 11
    Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED and Thompson EW. Epithelial–mesenchymal and mesenchymal– epithelial transitions in carcinoma progression. Journal of Cellular Physiology 2007; 213: 374383.
  • 12
    Yang J and Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Developmental Cell 2008; 14: 818829.
  • 13
    Thiery JP and Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nature Reviews. Molecular Cell Biology 2006; 7: 131142.
  • 14
    Oft M, Akhurst RJ and Balmain A. Metastasis is driven by sequential elevation of H-ras and Smad2 levels. Nature Cell Biology 2002; 4: 487494.
  • 15
    Huber MA, Kraut N and Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Current Opinion in Cell Biology 2005; 17: 548558.
  • 16
    Moustakas A and Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Science 2007; 98: 15121520.
  • 17
    Katoh Y and Katoh M. Hedgehog signaling, epithelial-to-mesenchymal transition and miRNA (review). International Journal of Molecular Medicine 2008; 22: 271275.
  • 18
    Singh A and Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29: 47414751.
  • 19
    Derynck R, Akhurst RJ and Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nature Genetics 2001; 29: 117129.
  • 20
    Blobe GC, Schiemann WP and Lodish HF. Role of transforming growth factor beta in human disease. The New England Journal of Medicine 2000; 342: 13501358.
  • 21
    Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW and Vogelstein B. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995; 268: 13361338.
  • 22
    Myeroff LL, Parsons R, Kim SJ, Hedrick L, Cho KR, Orth K, Mathis M, Kinzler KW, Lutterbaugh J,Park K, Bang YJ, Lee HY, Park JG, Lynch HT, Roberts AB, Vogelstein B and Markowitz SD. A transforming growth factor beta receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Research 1995; 55: 55455547.
  • 23
    Gal A, Sjöblom T, Fedorova L, Imreh S, Beug H and Moustakas A. Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis. Oncogene 2008; 27: 12181230.
  • 24
    Remy I, Montmarquette A and Michnick SW. PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nature Cell Biology 2004; 6: 358365.
  • 25
    Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nicolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS and Polyak K. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007; 11: 259273.
  • 26
    Wendt MK, Allington TM and Schiemann WP. Mechanisms of the epithelial-mesenchymal transition by TGF-beta. Future Oncology 2009; 5: 11451168.
  • 27
    Levy L and Hill CS. Smad4 dependency defines two classes of transforming growth factor {beta} (TGF-{beta}) target genes and distinguishes TGF-{beta}-induced epithelial-mesenchymal transition from its antiproliferative and migratory responses. Molecular and Cellular Biology 2005; 25: 81088125.
  • 28
    Verschueren K, Remacle JE, Collart C, Kraft H, Baker BS, Tylzanowski P, Nelles L, Wuytens G, Su MT, Bodmer R, Smith JC and Huylebroeck D. SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5-CACCT sequences in candidate target genes. The Journal of Biological Chemistry 1999; 274: 2048920498.
  • 29
    Huber MA, Azoitei N, Baumann B, Grünert S, Sommer A, Pehamberger H, Kraut N, Beug H and Wirth T. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. The Journal of Clinical Investigation 2004; 114: 569581.
  • 30
    Huang S, Pettaway CA, Uehara H, Bucana CD and Fidler IJ. Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene 2001; 20: 41884197.
  • 31
    Huang S, DeGuzman A, Bucana CD and Fidler IJ. Nuclear factor-kappaB activity correlates with growth, angiogenesis, and metastasis of human melanoma cells in nude mice. Clinical Cancer Research 2000; 6: 25732581.
  • 32
    Wu Y and Zhou BP. TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion. British Journal of Cancer 2010; 102: 639644.
  • 33
    Lehmann K, Janda E, Pierreux CE, Rytömaa M, Schulze A, McMahon M, Hill CS, Beug H and Downward J. Raf induces TGFbeta production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells. Genes and Development 2000; 14: 26102622.
  • 34
    Weinberg RA. Twisted epithelial-mesenchymal transition blocks senescence. Nature Cell Biology 2008; 10: 10211023.
  • 35
    Schmalhofer O, Brabletz S and Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Reviews 2009; 28: 151166.
  • 36
    Acloque H, Thiery JP and Nieto MA. The physiology and pathology of the EMT. Meeting on the epithelial-mesenchymal transition. EMBO Reports 2008; 9: 322326.
  • 37
    Brabletz T, Hlubek F, Spaderna S, Schmalhofer O, Hiendlmeyer E, Jung A and Kirchner T. Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs 2005; 179: 5665.
  • 38
    Williams CM, Engler AJ, Slone RD, Galante LL and Schwarzbauer JE. Fibronectin expression modulates mammary epithelial cell proliferation during acinar differentiation. Cancer Research 2008; 68: 31853192.
  • 39
    Darribere T and Schwarzbauer JE. Fibronectin matrix composition and organization can regulate cell migration during amphibian development. Mechanisms of Development 2000; 92: 239250.
  • 40
    Hao X, Sun B, Hu L, Lähdesmäki H, Dunmire V, Feng Y, Zhang SW, Wang H, Wu C, Wang H, Fuller GN, Symmans WF, Schmulevich I and Zhang W. Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis. Cancer 2004; 100: 11101122.
  • 41
    Seki K, Fujimori T, Savagner P, Hata A, Aikawa T, Ogata N, Nabeshima Y and Kaechoong L. Mouse Snail family transcription repressors regulate chondrocyte, extracellular matrix, type II collagen, and aggrecan. The Journal of Biological Chemistry 2003; 278: 4186241870.
  • 42
    Boulay JL, Dennefeld C and Alberga A. The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers. Nature 1987; 330: 395398.
  • 43
    Hemavathy K, Ashraf SI and Ip YT. Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene 2000; 257: 112.
  • 44
    Arias AM. Epithelial mesenchymal interactions in cancer and development. Cell 2001; 105: 425431.
  • 45
    Sugimachi K, Tanaka S, Kameyama T, Taguchi K, Aishima S, Shimada M, Sugimachi K and Tsuneyoshi M. Transcriptional repressor snail and progression of human hepatocellular carcinoma. Clinical Cancer Research 2003; 9: 26572664.
  • 46
    Hajra KM, Chen DY and Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Research 2002; 62: 16131618.
  • 47
    Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M and Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. Journal of Cell Science 2003; 116(Pt 3): 499511.
  • 48
    Olmeda D, Moreno-Bueno G, Flores JM, Fabra A, Portillo F and Cano A. SNAI1 is required for tumor growth and lymph node metastasis of human breast carcinoma MDA-MB-231 cells. Cancer Research 2007; 67: 1172111731.
  • 49
    Maestro R, Dei Tos AP, Hamamori Y, Krasnokutsky S, Sartorelli V, Kedes L, Doglioni C, Beach DH and Hannon GJ. Twist is a potential oncogene that inhibits apoptosis. Genes and Development 1999; 13: 22072217.
  • 50
    Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A and Weinberg RA. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004; 117: 927939.
  • 51
    Peinado H, Olmeda D and Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature Reviews Cancer 2007; 7: 415428.
  • 52
    Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, Berx G, Cano A, Beug H and Foisner R. DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene 2005; 24: 23752385.
  • 53
    Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D and van Roy F. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Molecules and Cells 2001; 7: 12671278.
  • 54
    Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S and Brabletz T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Reports 2008; 9: 582589.
  • 55
    Zeisberg M and Neilson EG. Biomarkers for epithelial-mesenchymal transitions. The Journal of Clinical Investigation 2009; 119: 14291437.
  • 56
    Reya T, Morrison SJ, Clarke MF and Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105111.
  • 57
    Nowell PC. The clonal evolution of tumor cell populations. Science 1976; 194: 2328.
  • 58
    Winquist RJ, Boucher DM, Wood M and Furey BF. Targeting cancer stem cells for more effective therapies: taking out cancer's locomotive engine. Biochemical Pharmacology 2009; 78: 326334.
  • 59
    Eyler CE and Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. Journal of Clinical Oncology 2008; 26: 28392845.
  • 60
    Dalerba P, Cho RW and Clarke MF. Cancer stem cells: models and concepts. Annual Review of Medicine 2007; 58: 267284.
  • 61
    Bonnet D and Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine 1997; 3: 730737.
  • 62
    Hope KJ, Jin L and Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nature Immunology 2004; 5: 738743.
  • 63
    Lapidot T, Sirard C, Vormoor J, Murdoch B,Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA and Dick JE. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367: 645648.
  • 64
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 2003; 100: 39833988.
  • 65
    O'Brien CA, Pollett A, Gallinger S and Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445: 106110.
  • 66
    Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R. Identification and expansion of human colon-cancer-initiating cells. Nature 2007; 445: 111115.
  • 67
    Singh SK, Hawkins C, Clarke ID, Squire JA,Bayani J, Hide T, Henkelman RM, Cusimano MD and Dirks PB. Identification of human brain tumour initiating cells. Nature 2004; 432: 396401.
  • 68
    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 and Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133: 704715.
  • 69
    Gupta PB, Chaffer CL and Weinberg RA. Cancer stem cells: mirage or reality? Nature Medicine 2009; 15: 10101012.
  • 70
    Morel AP, Lievre M, Thomas C, Hinkal G,Ansieau S and Puisieux A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008; 3: e2888.
  • 71
    Polyak K and Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nature Reviews Cancer 2009; 9: 265273.
  • 72
    Battula VL, Evans KW, Hollier BG, Shi Y,Marini FC, Ayyanan A, Wang R, Brisken C,Guerra R, Andreeff M and Mani SA. Epithelial-mesenchymal transition-derived cells exhibit multi-lineage differentiation potential similar to mesenchymal stem cells. Stem Cells 2010; 28: 14351445.
  • 73
    Pardal R, Clarke MF and Morrison SJ. Applying the principles of stem-cell biology to cancer. Nature Reviews Cancer 2003; 3: 895902.
  • 74
    Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J and Chang JC. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. Journal of the National Cancer Institute 2008; 100: 672679.
  • 75
    Blacking TM, Wilson H and Argyle DJ. Is cancer a stem cell disease? Theory, evidence and implications. Veterinary and Comparative Oncology 2007; 5: 7689.
  • 76
    Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M and Stoffel M. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005; 438: 685689.
  • 77
    Olmeda D, Jorda M, Peinado H, Fabra A andCano A. Snail silencing effectively suppresses tumour growth and invasiveness. Oncogene 2007; 26: 18621874.
  • 78
    Yan LX, Wu QN, Zhang Y, Li YY, Liao DZ, Hou JH, Fu J, Zeng MS, Yun JP, Wu QL, Zeng YX andShao JY. Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivo tumor growth. Breast Cancer Research 2011; 13: R2.
  • 79
    Graf T and Enver T. Forcing cells to change lineages. Nature 2009; 462: 587594.
  • 80
    Sanges D and Cosma MP. Reprogramming cell fate to pluripotency: the decision-making signalling pathways. The International Journal of Developmental Biology 2010; 54: 15751587.
  • 81
    Lowry WE. E-cadherin, a new mixer in the Yamanaka cocktail. EMBO Reports 2011; 12: 613614.
  • 82
    Takahashi K and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663676.
  • 83
    Stadtfeld M, Maherali N, Breault DT and Hochedlinger K. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2008; 2: 230240.
  • 84
    Redmer T, Diecke S, Grigoryan T, Quiroga-Negreira A, Birchmeier W and Besser D. E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming. EMBO Reports 2011; 12: 720726.
  • 85
    Liao B, Bao X, Liu L, Feng S, Zovoilis A, Liu W,Xue Y, Cai J, Guo X, Qin B, Zhang R, Wu J, Lai L, Teng M, Niu L, Zhang B, Esteban MA and Pei D. MicroRNA cluster 302-367 enhances somatic cell reprogramming by accelerating a mesenchymal-to-epithelial transition. The Journal of Biological Chemistry 2011; 286: 1735917364.
  • 86
    Chandler HL, Colitz CM, Lu P, Saville WJ and Kusewitt DF. The role of the slug transcription factor in cell migration during corneal re-epithelialization in the dog. Experimental Eye Research 2007; 84: 400411.
  • 87
    Aresu L, Rastaldi MP, Pregel P, Valenza F, Radaelli E, Scanziani E and Castagnaro M. Dog as model for down-expression of E-cadherin and beta-catenin in tubular epithelial cells in renal fibrosis. Virchows Archiv 2008; 453: 617625.
  • 88
    Aresu L, Rastaldi MP, Scanziani E, Baily J,Radaelli E, Pregel P and Valenza F. Epithelial-mesenchymal transition (EMT) of renal tubular cells in canine glomerulonephritis. Virchows Archiv 2007; 451: 937942.
  • 89
    Han JI, Kim DY and Na KJ. Dysregulation of the Wnt/beta-catenin signaling pathway in canine cutaneous melanotic tumor. Veterinary Pathology 2010; 47: 285291.
  • 90
    Larue L and Delmas V. The WNT/Beta-catenin pathway in melanoma. Frontiers in Bioscience 2006; 11: 733742.
  • 91
    McEntee MF and Brenneman KA. Dysregulation of beta-catenin is common in canine sporadic colorectal tumors. Veterinary Pathology 1999; 36: 228236.
  • 92
    Stein TJ, Holmes KE, Muthuswamy A, Thompson V and Huelsmeyer MK. Characterization of beta-catenin expression in canine osteosarcoma. Veterinary and Comparative Oncology 2011; 9: 6573.
  • 93
    Nowak M, Madej JA and Dziegiel P. Expression of E-cadherin, beta-catenin and Ki-67 antigen and their reciprocal relationships in mammary adenocarcinomas in bitches. Folia Histochemica et Cytobiologica 2007; 45: 233238.
  • 94
    Nowak M, Madej JA, Podhorska-Okolow M and Dziegiel P. Expression of extracellular matrix metalloproteinase (MMP-9), E-cadherin and proliferation-associated antigen Ki-67 and their reciprocal correlation in canine mammary adenocarcinomas. In Vivo 2008; 22: 463469.
  • 95
    Aresu L, Pregel P, Zanetti R, Caliari D, Biolatti B and Castagnaro M. E-cadherin and beta-catenin expression in canine colorectal adenocarcinoma. Research in Veterinary Science 2010; 89: 409414.
  • 96
    Ide T, Uchida K, Suzuki K, Kagawa Y and Nakayama H. Expression of cell adhesion molecules and doublecortin in canine anaplastic meningiomas. Veterinary Pathology 2011; 48: 292301.
  • 97
    Pang LY, Cervantes-Arias A and Argyle DJ. Canine mammary cancer stem cells are radio- and chemo-resistant and exhibit an epithelial-mesenchymal transition phenotype. Cancers 2011; 3: 17441762.