The rejuvenated scenario of epithelial-mesenchymal transition (EMT) and cancer metastasis

Cancer and Metastasis Reviews

Volumn 31, Issue 3-4, 2012, Pages 455-467

  Meng, Fanyan ^a,b   Wu, Guojun ^a,b,c  

^a KARMANOS CANCER INSTITUTE   (United States)

^b WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c WAYNE STATE UNIVERSITY   (United States)

Author keywords

Chemoresistance; EMT; Metastasis; Stem cell

Indexed keywords

ANTINEOPLASTIC AGENT; ARTESUNATE; BETA CATENIN; CYCLOPAMINE; CYTOKERATIN 18; ERLOTINIB; FIBROBLAST GROWTH FACTOR; GEFITINIB; HEPATOCYTE NUCLEAR FACTOR 3BETA; IPI 269609; JANUS KINASE; KRUPPEL LIKE FACTOR 4; LAPATINIB; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE P38; MUCIN; NERVE CELL ADHESION MOLECULE; NOTCH RECEPTOR; OXALIPLATIN; PACLITAXEL; PLAKOGLOBIN; PLATELET DERIVED GROWTH FACTOR; SMAD3 PROTEIN; SMOOTH MUSCLE ACTIN; STAT1 PROTEIN; TRANSCRIPTION FACTOR ZEB1; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG;

ARTICLE; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER STEM CELL; CELL ADHESION; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL DIFFERENTIATION; CELL ISOLATION; CELL JUNCTION; COLORECTAL CANCER; COMPETITIVE INHIBITION; CORRELATION ANALYSIS; CYTOSKELETON; DIMERIZATION; DISTANT METASTASIS; DNA METHYLATION; EMBRYO DEVELOPMENT; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; EXTRACELLULAR MATRIX; HEAD AND NECK CANCER; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HISTONE ACETYLATION; HUMAN; LUNG METASTASIS; LUNG NON SMALL CELL CANCER; MELANOMA; METASTASIS; MOLECULAR INTERACTION; NONHUMAN; PANCREAS CANCER; PHENOTYPE; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN SECRETION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; TROPHOBLAST; TUMOR MICROENVIRONMENT; UPREGULATION; WESTERN BLOTTING;

ANIMALS; DNA METHYLATION; DRUG RESISTANCE, NEOPLASM; EPITHELIAL-MESENCHYMAL TRANSITION; HISTONES; HUMANS; MICRORNAS; NEOPLASM METASTASIS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; TRANSFORMING GROWTH FACTOR BETA;

EID: 84867985560     PISSN: 01677659     EISSN: 15737233     Source Type: Journal    
DOI: 10.1007/s10555-012-9379-3     Document Type: Article

References (138)

1. Acloque, H.; Thiery, J. P.; & Nieto, M. A. (2008). The physiology and pathology of the EMT. EMBO Reports, 9(4), 322-326. doi: 10.1038/embor.2008.30.
2. Baum, B.; Settleman, J.; & Quinlan, M. P. (2008). Transitions between epithelial and mesenchymal states in development and disease. Seminars in Cell & Developmental Biology, 19(3), 294-308. doi: 10.1016/j.semcdb.2008.02.001.
3. Thiery, J. P. (2002). Epithelial-mesenchymal transitions in tumour progression. Nature Reviews. Cancer, 2(6), 442-454. doi: 10.1038/nrc822nrc822.
4. Thiery, J. P.; & Sleeman, J. P. (2006). Complex networks orchestrate epithelial-mesenchymal transitions. Nature Reviews Molecular Cell Biology, 7(2), 131-142. doi: 10.1038/nrm1835.
5. Yang, J.; & Weinberg, R. A. (2008). Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Developmental Cell, 14(6), 818-829. doi: 10.1016/j.devcel.2008.05.009.
6. Davies, J. A. (1996). Mesenchyme to epithelium transition during development of the mammalian kidney tubule. Acta Anat (Basel), 156(3), 187-201.
7. Voulgari, A.; & Pintzas, A. (2009). Epithelial-mesenchymal transition in cancer metastasis: Mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochimica et Biophysica Acta, 1796(2), 75-90. doi: 10.1016/j.bbcan.2009.03.002.
8. Barr, S.; Thomson, S.; Buck, E.; Russo, S.; Petti, F.; Sujka-Kwok, I.; et al. (2008). Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clinical & Experimental Metastasis, 25(6), 685-693. doi: 10.1007/s10585-007-9121-7.
9. Huber, M. A.; Kraut, N.; & Beug, H. (2005). Molecular requirements for epithelial-mesenchymal transition during tumor progression. Current Opinion in Cell Biology, 17(5), 548-558. doi: 10.1016/j.ceb.2005.08.001.
10. Moustakas, A.; & Heldin, C. H. (2007). Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Science, 98(10), 1512-1520. doi: 10.1111/j.1349-7006.2007.00550.x.
11. Lo, H. W.; Hsu, S. C.; Xia, W.; Cao, X.; Shih, J. Y.; Wei, Y.; et al. (2007). Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Research, 67(19), 9066-9076. doi: 10.1158/0008-5472.CAN-07-0575.
12. Birchmeier, C.; Birchmeier, W.; Gherardi, E.; & Vande Woude, G. F. (2003). Met, metastasis, motility and more. Nature Reviews Molecular Cell Biology, 4(12), 915-925. doi: 10.1038/nrm1261nrm1261.
13. Boyer, B.; & Thiery, J. P. (1993). Cyclic AMP distinguishes between two functions of acidic FGF in a rat bladder carcinoma cell line. The Journal of Cell Biology, 120(3), 767-776.
14. Savagner, P.; Yamada, K. M.; & Thiery, J. P. (1997). The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. The Journal of Cell Biology, 137(6), 1403-1419.
15. Bellusci, S.; Moens, G.; Thiery, J. P.; & Jouanneau, J. (1994). A scatter factor-like factor is produced by a metastatic variant of a rat bladder carcinoma cell line. Journal of Cell Science, 107(Pt 5), 1277-1287.
16. Grotegut, S.; von Schweinitz, D.; Christofori, G.; & Lehembre, F. (2006). Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail. EMBO Journal, 25(15), 3534-3545. doi: 10.1038/sj.emboj.7601213.
17. Min, C.; Eddy, S. F.; Sherr, D. H.; & Sonenshein, G. E. (2008). NF-kappaB and epithelial to mesenchymal transition of cancer. Journal of Cellular Biochemistry, 104(3), 733-744. doi: 10.1002/jcb.21695.
18. Taylor, M. A.; Parvani, J. G.; & Schiemann, W. P. (2010). The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells. Journal of Mammary Gland Biology and Neoplasia, 15(2), 169-190. doi: 10.1007/s10911-010- 9181-1.
19. Vincan, E.; & Barker, N. (2008). The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clinical & Experimental Metastasis, 25(6), 657-663. doi: 10.1007/s10585-008-9156-4.
20. Wang, Z.; Li, Y.; Kong, D.; & Sarkar, F. H. (2010). The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Current Drug Targets, 11(6), 745-751.
21. Wendt, M. K.; Allington, T. M.; & Schiemann, W. P. (2009). Mechanisms of the epithelial-mesenchymal transition by TGF-beta. Future Oncology, 5(8), 1145-1168. doi: 10.2217/fon.09.90.
22. Tian, M.; & Schiemann, W. P. (2009). The TGF-beta paradox in human cancer: an update. Future Oncology, 5(2), 259-271. doi: 10.2217/14796694.5.2. 259.
23. Tian, F.; DaCosta Byfield, S.; Parks, W. T.; Yoo, S.; Felici, A.; Tang, B.; et al. (2003). Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Research, 63(23), 8284-8292.
24. Tian, F.; Byfield, S. D.; Parks, W. T.; Stuelten, C. H.; Nemani, D.; Zhang, Y. E.; et al. (2004). Smad-binding defective mutant of transforming growth factor beta type I receptor enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Research, 64(13), 4523-4530. doi: 10.1158/0008-5472.CAN-04-003064/13/4523.
25. Deckers, M.; van Dinther, M.; Buijs, J.; Que, I.; Lowik, C.; van der Pluijm, G.; et al. (2006). The tumor suppressor Smad4 is required for transforming growth factor beta-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Research, 66(4), 2202-2209. doi: 10.1158/0008-5472.CAN-05-3560.
26. Kang, Y.; He, W.; Tulley, S.; Gupta, G. P.; Serganova, I.; Chen, C. R.; et al. (2005). Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proceedings of the National Academy of Sciences of the United States of America, 102(39), 13909-13914. doi: 10.1073/pnas.0506517102.
27. Hayashi, H.; Abdollah, S.; Qiu, Y.; Cai, J.; Xu, Y. Y.; Grinnell, B. W.; et al. (1997). The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell, 89(7), 1165-1173.
28. Souchelnytskyi, S.; Nakayama, T.; Nakao, A.; Moren, A.; Heldin, C. H.; Christian, J. L.; et al. (1998). Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. Journal of Biological Chemistry, 273(39), 25364-25370.
29. Azuma, H.; Ehata, S.; Miyazaki, H.; Watabe, T.; Maruyama, O.; Imamura, T.; et al. (2005). Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells. Journal of the National Cancer Institute, 97(23), 1734-1746. doi: 10.1093/jnci/dji399.
30. Leivonen, S. K.; Ala-Aho, R.; Koli, K.; Grenman, R.; Peltonen, J.; & Kahari, V. M. (2006). Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells. Oncogene, 25(18), 2588-2600. doi: 10.1038/sj.Onc.1209291.
31. Leivonen, S. K.; & Kahari, V. M. (2007). Transforming growth factor-beta signaling in cancer invasion and metastasis. International Journal of Cancer, 121(10), 2119-2124. doi: 10.1002/ijc.23113.
32. Javelaud, D.; Mohammad, K. S.; McKenna, C. R.; Fournier, P.; Luciani, F.; Niewolna, M.; et al. (2007). Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Research, 67(5), 2317-2324. doi: 10.1158/0008-5472.CAN-06-3950.
33. Janda, E.; Lehmann, K.; Killisch, I.; Jechlinger, M.; Herzig, M.; Downward, J.; et al. (2002). Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. The Journal of Cell Biology, 156(2), 299-313. doi: 10.1083/jcb.200109037jcb. 200109037.
34. Xie, L.; Law, B. K.; Chytil, A. M.; Brown, K. A.; Aakre, M. E.; & Moses, H. L. (2004). Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia, 6(5), 603-610. doi: 10.1593/neo.04241.
35. Neil, J. R.; Johnson, K. M.; Nemenoff, R. A.; & Schiemann, W. P. (2008). Cox-2 inactivates Smad signaling and enhances EMT stimulated by TGF-beta through a PGE2-dependent mechanisms. Carcinogenesis, 29(11), 2227-2235. doi: 10.1093/carcin/bgn202.
36. Bhowmick, N. A.; Zent, R.; Ghiassi, M.; McDonnell, M.; & Moses, H. L. (2001). Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. Journal of Biological Chemistry, 276(50), 46707-46713. doi: 10.1074/jbc. M106176200M106176200.
37. Galliher, A. J.; & Schiemann, W. P. (2006). Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial-mesenchymal transition in mammary epithelial cells. Breast Cancer Research, 8(4), R42. doi: 10.1186/bcr1524.
38. Galliher-Beckley, A. J.; & Schiemann, W. P. (2008). Grb2 binding to Tyr284 in TbetaR-II is essential for mammary tumor growth and metastasis stimulated by TGF-beta. Carcinogenesis, 29(2), 244-251. doi: 10.1093/carcin/bgm245.
39. Miele, L. (2006). Notch signaling. Clinical Cancer Research, 12(4), 1074-1079. doi: 10.1158/1078-0432.CCR-05-2570.
40. Miele, L.; & Osborne, B. (1999). Arbiter of differentiation and death: Notch signaling meets apoptosis. Journal of Cellular Physiology, 181(3), 393-409. doi:10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6 [pii]10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6.
41. Niessen, K.; Fu, Y.; Chang, L.; Hoodless, P. A.; McFadden, D.; & Karsan, A. (2008). Slug is a direct Notch target required for initiation of cardiac cushion cellularization. The Journal of Cell Biology, 182(2), 315-325. doi: 10.1083/jcb.200710067.
42. Zavadil, J.; Cermak, L.; Soto-Nieves, N.; & Bottinger, E. P. (2004). Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO Journal, 23(5), 1155-1165. doi: 10.1038/sj.emboj.76000697600069.
43. Niimi, H.; Pardali, K.; Vanlandewijck, M.; Heldin, C. H.; & Moustakas, A. (2007). Notch signaling is necessary for epithelial growth arrest by TGF-beta. The Journal of Cell Biology, 176(5), 695-707. doi: 10.1083/jcb.200612129.
44. Jechlinger, M.; Sommer, A.; Moriggl, R.; Seither, P.; Kraut, N.; Capodiecci, P.; et al. (2006). Autocrine PDGFR signaling promotes mammary cancer metastasis. The Journal of Clinical Investigation, 116(6), 1561-1570. doi: 10.1172/JCI24652.
45. Fischer, A. N.; Fuchs, E.; Mikula, M.; Huber, H.; Beug, H.; & Mikulits, W. (2007). PDGF essentially links TGF-beta signaling to nuclear beta-catenin accumulation in hepatocellular carcinoma progression. Oncogene, 26(23), 3395-3405. doi: 10.1038/sj.onc.1210121.
46. Gotzmann, J.; Fischer, A. N.; Zojer, M.; Mikula, M.; Proell, V.; Huber, H.; et al. (2006). A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes. Oncogene, 25(22), 3170-3185. doi: 10.1038/sj.onc.1209083.
47. Zhao, J. H.; Luo, Y.; Jiang, Y. G.; He, D. L.; & Wu, C. T. (2011). Knockdown of beta-catenin through shRNA cause a reversal of EMT and metastatic phenotypes induced by HIF-1alpha. Cancer Investigation, 29(6), 377-382. doi: 10.3109/07357907.2010.512595.
48. Cheng, Z. X.; Sun, B.; Wang, S. J.; Gao, Y.; Zhang, Y. M.; Zhou, H. X.; et al. (2011). Nuclear factor-kappaB-dependent epithelial to mesenchymal transition induced by HIF-1alpha activation in pancreatic cancer cells under hypoxic conditions. PLoS One, 6(8), e23752. doi: 10.1371/journal.pone. 0023752PONE-D-11-07211.
49. Batlle, E.; Sancho, E.; Franci, C.; Dominguez, D.; Monfar, M.; Baulida, J.; et al. (2000). The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature Cell Biology, 2(2), 84-89. doi: 10.1038/35000034.
50. Cano, A.; Perez-Moreno, M. A.; Rodrigo, I.; Locascio, A.; Blanco, M. J.; del Barrio, M. G.; et al. (2000). The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology, 2(2), 76-83. doi: 10.1038/35000025.
51. Hajra, K. M.; Chen, D. Y.; & Fearon, E. R. (2002). The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Research, 62(6), 1613-1618.
52. Comijn, J.; Berx, G.; Vermassen, P.; Verschueren, K.; van Grunsven, L.; Bruyneel, E.; et al. (2001). The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Molecular Cell, 7(6), 1267-1278. doi: S1097-2765(01)00260-X.
53. Eger, A.; Aigner, K.; Sonderegger, S.; Dampier, B.; Oehler, S.; Schreiber, M.; et al. (2005). DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene, 24(14), 2375-2385. doi: 10.1038/sj.onc.1208429.
54. Remacle, J. E.; Kraft, H.; Lerchner, W.; Wuytens, G.; Collart, C.; Verschueren, K.; et al. (1999). New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites. EMBO Journal, 18(18), 5073-5084. doi: 10.1093/emboj/18.18.5073.
55. Yang, J.; Mani, S. A.; Donaher, J. L.; Ramaswamy, S.; Itzykson, R. A.; Come, C.; et al. (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 117(7), 927-939. doi: 10.1016/j.cell.2004.06.006S0092867404005768.
56. Katoh, M. (2004). Human FOX gene family (review). International Journal of Oncology, 25(5), 1495-1500.
57. Mani, S. A.; Yang, J.; Brooks, M.; Schwaninger, G.; Zhou, A.; Miura, N.; et al. (2007). Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proceedings of the National Academy of Sciences of the United States of America, 104(24), 10069-10074. doi: 10.1073/pnas.0703900104.
58. Bloushtain-Qimron, N.; Yao, J.; Snyder, E. L.; Shipitsin, M.; Campbell, L. L.; Mani, S. A.; et al. (2008). Cell type-specific DNA methylation patterns in the human breast. Proceedings of the National Academy of Sciences of the United States of America, 105(37), 14076-14081. doi: 10.1073/pnas.0805206105.
59. Ray, P. S.; Wang, J.; Qu, Y.; Sim, M. S.; Shamonki, J.; Bagaria, S. P.; et al. (2010). FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer Research, 70(10), 3870-3876. doi: 10.1158/0008-5472.CAN-09-4120.
60. Feuerborn, A.; Srivastava, P. K.; Kuffer, S.; Grandy, W. A.; Sijmonsma, T. P.; Gretz, N.; et al. (2011). The Forkhead factor FoxQ1 influences epithelial differentiation. Journal of Cellular Physiology, 226(3), 710-719. doi: 10.1002/jcp. 22385.
61. Qiao, Y.; Jiang, X.; Lee, S. T.; Karuturi, R. K.; Hooi, S. C.; & Yu, Q. (2011). FOXQ1 regulates epithelial-mesenchymal transition in human cancers. Cancer Research, 71(8), 3076-3086. doi: 10.1158/0008-5472.CAN-10-2787.
62. Zhang, H.; Meng, F.; Liu, G.; Zhang, B.; Zhu, J.; Wu, F.; et al. (2011). Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis. Cancer Research, 71(4), 1292-1301. doi: 10.1158/0008-5472.CAN-10-2825.
63. Tang, Y.; Shu, G.; Yuan, X.; Jing, N.; & Song, J. (2011). FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers. Cell Research, 21(2), 316-326. doi: 10.1038/cr.2010.126.
64. Yori, J. L.; Johnson, E.; Zhou, G.; Jain, M. K.; & Keri, R. A. (2010). Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression. Journal of Biological Chemistry, 285(22), 16854-16863. doi: 10.1074/jbc.M110.114546.
65. Gumireddy, K.; Li, A.; Gimotty, P. A.; Klein-Szanto, A. J.; Showe, L. C.; Katsaros, D.; et al. (2009). KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer. Nature Cell Biology, 11(11), 1297-1304. doi: 10.1038/ncb1974.
66. Wang, X.; Zheng, M.; Liu, G.; Xia, W.; McKeown-Longo, P. J.; Hung, M. C.; et al. (2007). Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Research, 67(15), 7184-7193. doi: 10.1158/0008-5472.CAN-06-4729.
67. Holian, J.; Qi, W.; Kelly, D. J.; Zhang, Y.; Mreich, E.; Pollock, C. A.; et al. (2008). Role of Kruppel-like factor 6 in transforming growth factor-beta1-induced epithelial-mesenchymal transition of proximal tubule cells. American Journal of Physiology. Renal Physiology, 295(5), F1388-F1396. doi: 10.1152/ajprenal.00055.2008.
68. Yu, M.; Smolen, G. A.; Zhang, J.; Wittner, B.; Schott, B. J.; Brachtel, E.; et al. (2009). A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression. Genes & Development, 23(15), 1737-1742. doi: 10.1101/gad.1809309.
69. Evdokimova, V.; Tognon, C.; Ng, T.; Ruzanov, P.; Melnyk, N.; Fink, D.; et al. (2009). Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer Cell, 15(5), 402-415. doi: 10.1016/j.ccr.2009.03.017.
70. Fernando, R. I.; Litzinger, M.; Trono, P.; Hamilton, D. H.; Schlom, J.; & Palena, C. (2010). The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells. The Journal of Clinical Investigation, 120(2), 533-544. doi: 10.1172/JCI38379.
71. Beltran, M.; Puig, I.; Pena, C.; Garcia, J. M.; Alvarez, A. B.; Pena, R.; et al. (2008). A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes & Development, 22(6), 756-769. doi: 10.1101/gad.455708.
72. Cano, A.; & Nieto, M. A. (2008). Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends in Cell Biology, 18(8), 357-359. doi: 10.1016/j.tcb.2008.05.005.
73. Gregory, P. A.; Bert, A. G.; Paterson, E. L.; Barry, S. C.; Tsykin, A.; Farshid, G.; et al. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology, 10(5), 593-601. doi: 10.1038/ncb1722.
74. Gregory, P. A.; Bracken, C. P.; Bert, A. G.; & Goodall, G. J. (2008). MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle, 7(20), 3112-3118.
75. Park, S. M.; Gaur, A. B.; Lengyel, E.; & Peter, M. E. (2008). The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes & Development, 22(7), 894-907. doi: 10.1101/gad.1640608.
76. Gebeshuber, C. A.; Zatloukal, K.; & Martinez, J. (2009). miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Reports, 10(4), 400-405. doi: 10.1038/embor.2009.9.
77. Kong, W.; Yang, H.; He, L.; Zhao, J. J.; Coppola, D.; Dalton, W. S.; et al. (2008). MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Molecular and Cellular Biology, 28(22), 6773-6784. doi: 10.1128/MCB.00941-08.
78. Dong, P.; Kaneuchi, M.; Watari, H.; Hamada, J.; Sudo, S.; Ju, J.; et al. (2011). MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Molecular Cancer, 10, 99. doi: 10.1186/1476-4598-10-99.
79. Kumarswamy, R.; Mudduluru, G.; Ceppi, P.; Muppala, S.; Kozlowski, M.; Niklinski, J.; et al. (2012). MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. International Journal of Cancer, 130, 2044-2053. doi: 10.1002/ijc.26218.
80. Liu, X.; Wang, C.; Chen, Z.; Jin, Y.; Wang, Y.; Kolokythas, A.; et al. (2011). MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines. Biochemistry Journal, 440(1), 23-31. doi: 10.1042/BJ20111006.
81. Stinson, S.; Lackner, M. R.; Adai, A. T.; Yu, N.; Kim, H. J.; O'Brien, C.; et al. (2011). TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer. Science Signaling, 4(177), ra41. doi: 10.1126/scisignal.2001538.
82. Aigner, A. (2011). MicroRNAs (miRNAs) in cancer invasion and metastasis: Therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl), 89(5), 445-457. doi: 10.1007/s00109-010-0716-0.
83. Cortez, M. A.; Ivan, C.; Zhou, P.; Wu, X.; Ivan, M.; & Calin, G. A. (2010). microRNAs in cancer: From bench to bedside. Advances in Cancer Research, 108, 113-157. doi: 10.1016/B978-0-12-380888-2.00004-2.
84. Garofalo, M.; & Croce, C. M. (2011). microRNAs: Master regulators as potential therapeutics in cancer. Annual Review of Pharmacology and Toxicology, 51, 25-43. doi: 10.1146/annurev-pharmtox-010510-100517.
85. Wright, J. A.; Richer, J. K.; & Goodall, G. J. (2010). microRNAs and EMT in mammary cells and breast cancer. Journal of Mammary Gland Biology and Neoplasia, 15(2), 213-223. doi: 10.1007/s10911-010-9183-z.
86. Lombaerts, M.; van Wezel, T.; Philippo, K.; Dierssen, J. W.; Zimmerman, R. M.; Oosting, J.; et al. (2006). E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. British Journal of Cancer, 94(5), 661-671. doi: 10.1038/sj.bjc.6602996.
87. Tryndyak, V. P.; Beland, F. A.; & Pogribny, I. P. (2010). E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. International Journal of Cancer, 126(11), 2575-2583.
88. Vrba, L.; Jensen, T. J.; Garbe, J. C.; Heimark, R. L.; Cress, A. E.; Dickinson, S.; et al. (2010). Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One, 5(1), e8697.
89. Ke, X. S.; Qu, Y.; Cheng, Y.; Li, W. C.; Rotter, V.; Oyan, A. M.; et al. (2010). Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells. BMC Genomics, 11, 669. doi: 10.1186/1471-2164-11-669.
90. Bernstein, B. E.; Mikkelsen, T. S.; Xie, X.; Kamal, M.; Huebert, D. J.; Cuff, J.; et al. (2006). A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125(2), 315-326. doi: 10.1016/j.cell.2006. 02.041.
91. Cedar, H.; & Bergman, Y. (2009). Linking DNA methylation and histone modification: patterns and paradigms. Nature Reviews Genetics, 10(5), 295-304. doi: 10.1038/nrg2540.
92. Kaimori, A.; Potter, J. J.; Choti, M.; Ding, Z.; Mezey, E.; & Koteish, A. A. (2010). Histone deacetylase inhibition suppresses the transforming growth factor beta1-induced epithelial-to-mesenchymal transition in hepatocytes. Hepatology, 52(3), 1033-1045.
93. Yoshikawa, M.; Hishikawa, K.; Marumo, T.; & Fujita, T. (2007). Inhibition of histone deacetylase activity suppresses epithelial-to-mesenchymal transition induced by TGF-beta1 in human renal epithelial cells. Journal of the American Society of Nephrology, 18(1), 58-65.
94. Jordan, N. V.; Johnson, G. L.; & Abell, A. N. (2011). Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle, 10(17), 2865-2873.
95. Abell, A. N.; Jordan, N. V.; Huang, W.; Prat, A.; Midland, A. A.; Johnson, N. L.; et al. (2011). MAP3K4/CBP-regulated H2B acetylation controls epithelial-mesenchymal transition in trophoblast stem cells. Cell Stem Cell, 8(5), 525-537.
96. Wels, C.; Joshi, S.; Koefinger, P.; Bergler, H.; & Schaider, H. (2011). Transcriptional activation of ZEB1 by Slug leads to cooperative regulation of the epithelial-mesenchymal transition-like phenotype in melanoma. The Journal of Investigative Dermatology, 131(9), 1877-1885. doi: 10.1038/jid.2011.142.
97. Casas, E.; Kim, J.; Bendesky, A.; Ohno-Machado, L.; Wolfe, C. J.; & Yang, J. (2011). Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Research, 71(1), 245-254. doi: 10.1158/0008-5472.CAN-10-2330.
98. Taube, J. H.; Herschkowitz, J. I.; Komurov, K.; Zhou, A. Y.; Gupta, S.; Yang, J.; et al. (2010). Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proceedings of the National Academy of Sciences of the United States of America, 107(35), 15449-15454. doi: 10.1073/pnas.1004900107.
99. Chaffer, C. L.; Brennan, J. P.; Slavin, J. L.; Blick, T.; Thompson, E. W.; & Williams, E. D. (2006). Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Research, 66(23), 11271-11278. doi: 10.1158/0008-5472.CAN-06- 2044.
100. Korpal, M.; Ell, B. J.; Buffa, F. M.; Ibrahim, T.; Blanco, M. A.; Celia-Terrassa, T.; et al. (2011). Direct targeting of Sec23a by miR-200 s influences cancer cell secretome and promotes metastatic colonization. Nature Medicine, 17(9), 1101-1108. doi: 10.1038/nm.2401.
101. Chao, Y. L.; Shepard, C. R.; & Wells, A. (2010). Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Molecular Cancer, 9, 179.
102. Jeschke, U.; Mylonas, I.; Kuhn, C.; Shabani, N.; Kunert-Keil, C.; Schindlbeck, C.; et al. (2007). Expression of E-cadherin in human ductal breast cancer carcinoma in situ, invasive carcinomas, their lymph node metastases, their distant metastases, carcinomas with recurrence and in recurrence. Anticancer Research, 27(4A), 1969-1974.
103. Park, D.; Karesen, R.; Axcrona, U.; Noren, T.; & Sauer, T. (2007). Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7), their influence on survival in primary breast carcinoma, and their corresponding axillary lymph node metastasis. APMIS, 115(1), 52-65.
104. Christiansen, J. J.; & Rajasekaran, A. K. (2006). Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Research, 66(17), 8319-8326. doi: 10.1158/0008-5472.CAN- 06-0410.
105. Garber, K. (2008). Epithelial-to-mesenchymal transition is important to metastasis, but questions remain. Journal of the National Cancer Institute, 100(4), 232-233. doi: 10.1093/jnci/djn032.
106. Tarin, D.; Thompson, E. W.; & Newgreen, D. F. (2005). The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Research, 65(14), 5996-6000. doi: 10.1158/0008-5472.CAN-05-0699. discussion 6000-5991.
107. Thompson, E. W.; Newgreen, D. F.; & Tarin, D. (2005). Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Research, 65(14), 5991-5995. doi: 10.1158/0008-5472.CAN-05-0616. discussion 5995.
108. Aslakson, C. J.; & Miller, F. R. (1992). Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Research, 52(6), 1399-1405.
109. Zhang, H.; Meng, F.; Wu, S.; Kreike, B.; Sethi, S.; Chen, W.; et al. (2011). Engagement of I-branching beta}-1, 6-N-acetylglucosaminyltransferase 2 in breast cancer metastasis and TGF-{beta signaling. Cancer Research, 71(14), 4846-4856. doi: 10.1158/0008-5472.CAN-11-0414.
110. Lou, Y.; Preobrazhenska, O.; auf dem Keller, U.; Sutcliffe, M.; Barclay, L.; McDonald, P. C.; et al. (2008). Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis. Developmental Dynamics, 237(10), 2755-2768. doi: 10.1002/dvdy.21658.
111. Futterman, M. A.; Garcia, A. J.; & Zamir, E. A. (2011). Evidence for partial epithelial-to-mesenchymal transition (pEMT) and recruitment of motile blastoderm edge cells during avian epiboly. Developmental Dynamics, 240(6), 1502-1511. doi: 10.1002/dvdy.22607.
112. Chao, Y.; Wu, Q.; Acquafondata, M.; Dhir, R.; & Wells, A. (2011). Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases. Cancer Microenviron, 5, 19-28. doi: 10.1007/s12307-011-0085- 4.
113. Bruewer, M.; Hopkins, A. M.; Hobert, M. E.; Nusrat, A.; & Madara, J. L. (2004). RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and F-actin. American Journal of Physiology. Cell Physiology, 287(2), C327-C335. doi: 10.1152/ajpcell.00087.200400087.2004.
114. Hay, E. D.; & Zuk, A. (1995). Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. American Journal of Kidney Diseases, 26(4), 678-690. doi: 0272-6386(95)90610-X.
115. Pinkas, J.; & Leder, P. (2002). MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Research, 62(16), 4781-4790.
116. Xue, C.; Plieth, D.; Venkov, C.; Xu, C.; & Neilson, E. G. (2003). The gatekeeper effect of epithelial-mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Research, 63(12), 3386-3394.
117. Mani, S. A.; Guo, W.; Liao, M. J.; Eaton, E. N.; Ayyanan, A.; Zhou, A. Y.; et al. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704-715. doi: 10.1016/j.cell.2008.03. 027.
118. Morel, A. P.; Lievre, M.; Thomas, C.; Hinkal, G.; Ansieau, S.; & Puisieux, A. (2008). Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One, 3(8), e2888. doi: 10.1371/journal.pone.0002888.
119. Aktas, B.; Tewes, M.; Fehm, T.; Hauch, S.; Kimmig, R.; & Kasimir-Bauer, S. (2009). Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Research, 11(4), R46. doi: 10.1186/bcr2333.
120. Raimondi, C.; Gradilone, A.; Naso, G.; Vincenzi, B.; Petracca, A.; Nicolazzo, C.; et al. (2011). Epithelial-mesenchymal transition and stemness features in circulating tumor cells from breast cancer patients. Breast Cancer Research and Treatment, 130(2), 449-455. doi: 10.1007/s10549-011-1373-x.
121. Kallergi, G.; Papadaki, M. A.; Politaki, E.; Mavroudis, D.; Georgoulias, V.; & Agelaki, S. (2011). Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Research, 13(3), R59. doi: 10.1186/bcr2896.
122. Armstrong, A. J.; Marengo, M. S.; Oltean, S.; Kemeny, G.; Bitting, R. L.; Turnbull, J. D.; et al. (2011). Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Molecular Cancer Research, 9(8), 997-1007. doi: 10.1158/1541-7786.MCR- 10-0490.
123. Li, R.; Liang, J.; Ni, S.; Zhou, T.; Qing, X.; Li, H.; et al. (2010). A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell, 7(1), 51-63. doi: 10.1016/j.stem.2010.04.014.
124. Samavarchi-Tehrani, P.; Golipour, A.; David, L.; Sung, H. K.; Beyer, T. A.; Datti, A.; et al. (2010). Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell, 7(1), 64-77. doi: 10.1016/j.stem.2010.04.015.
125. Blick, T.; Widodo, E.; Hugo, H.; Waltham, M.; Lenburg, M. E.; Neve, R. M.; et al. (2008). Epithelial mesenchymal transition traits in human breast cancer cell lines. Clinical & Experimental Metastasis, 25(6), 629-642. doi: 10.1007/s10585-008-9170-6.
126. Neve, R. M.; Chin, K.; Fridlyand, J.; Yeh, J.; Baehner, F. L.; Fevr, T.; et al. (2006). A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell, 10(6), 515-527. doi: 10.1016/j.ccr.2006.10.008.
127. Sayan, A. E.; Griffiths, T. R.; Pal, R.; Browne, G. J.; Ruddick, A.; Yagci, T.; et al. (2009). SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proceedings of the National Academy of Sciences of the United States of America, 106(35), 14884-14889. doi: 10.1073/pnas.0902042106.
128. Fuchs, B. C.; Fujii, T.; Dorfman, J. D.; Goodwin, J. M.; Zhu, A. X.; Lanuti, M.; et al. (2008). Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Research, 68(7), 2391-2399. doi: 10.1158/0008-5472.CAN-07-2460.
129. Li, L. N.; Zhang, H. D.; Yuan, S. J.; Yang, D. X.; Wang, L.; & Sun, Z. X. (2008). Differential sensitivity of colorectal cancer cell lines to artesunate is associated with expression of beta-catenin and E-cadherin. European Journal of Pharmacology, 588(1), 1-8. doi: 10.1016/j.ejphar.2008.03. 041.
130. Sokol, J. P.; Neil, J. R.; Schiemann, B. J.; & Schiemann, W. P. (2005). The use of cystatin C to inhibit epithelial-mesenchymal transition and morphological transformation stimulated by transforming growth factor-beta. Breast Cancer Research, 7(5), R844-R853. doi: 10.1186/bcr1312.
131. Feldmann, G.; Dhara, S.; Fendrich, V.; Bedja, D.; Beaty, R.; Mullendore, M.; et al. (2007). Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: A new paradigm for combination therapy in solid cancers. Cancer Research, 67(5), 2187-2196. doi: 10.1158/0008-5472.CAN-06-3281.
132. Feldmann, G.; Fendrich, V.; McGovern, K.; Bedja, D.; Bisht, S.; Alvarez, H.; et al. (2008). An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Molecular Cancer Therapeutics, 7(9), 2725-2735. doi: 10.1158/1535-7163.MCT-08- 0573.
133. Yauch, R. L.; Januario, T.; Eberhard, D. A.; Cavet, G.; Zhu, W.; Fu, L.; et al. (2005). Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clinical Cancer Research, 11(24 Pt 1), 8686-8698. doi: 10.1158/1078-0432.CCR- 05-1492.
134. Kajiyama, H.; Shibata, K.; Terauchi, M.; Yamashita, M.; Ino, K.; Nawa, A.; et al. (2007). Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. International Journal of Oncology, 31(2), 277-283.
135. Konecny, G. E.; Venkatesan, N.; Yang, G.; Dering, J.; Ginther, C.; Finn, R.; et al. (2008). Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells. British Journal of Cancer, 98(6), 1076-1084. doi: 10.1038/sj.bjc.6604278.
136. Yang, Y.; Pan, X.; Lei, W.; Wang, J.; & Song, J. (2006). Transforming growth factor-beta1 induces epithelial-to-mesenchymal transition and apoptosis via a cell cycle-dependent mechanism. Oncogene, 25(55), 7235-7244.
137. Vega, S.; Morales, A. V.; Ocana, O. H.; Valdes, F.; Fabregat, I.; & Nieto, M. A. (2004). Snail blocks the cell cycle and confers resistance to cell death. Genes & Development, 18(10), 1131-1143.
138. Mejlvang, J.; Kriajevska, M.; Vandewalle, C.; Chernova, T.; Sayan, A. E.; Berx, G.; et al. (2007). Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition. Molecular Biology of the Cell, 18(11), 4615-4624.