[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.4062/biomolther.2021.178

Epithelial-Mesenchymal Transition-Inducing Factors Involved in the Progression of Lung Cancers

Nam, Min-Woo (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
Kim, Cho-Won (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
Choi, Kyung-Chul (Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)

Publication Information

Biomolecules & Therapeutics / v.30, no.3, 2022 , pp. 213-220 More about this Journal

Abstract

Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelial-mesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.

Keywords

EMT; Lung cancer; Metastasis; FOXC2; E-cadherin; N-cadherin; Snail;

Citations & Related Records

Reference

1	Acloque, H., Adams, M. S., Fishwick, K., Bronner-Fraser, M. and Nieto, M. A. (2009) Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J. Clin. Invest. 119, 1438-1449. DOI
2	Barbera, M. J., Puig, I., Dominguez, D., Julien-Grille, S., Guaita-Esteruelas, S., Peiro, S., Baulida, J., Franci, C., Dedhar, S., Larue, L. and Garcia de Herreros, A. (2004) Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene 23, 7345-7354. DOI
3	De Craene, B., Gilbert, B., Stove, C., Bruyneel, E., van Roy, F. and Berx, G. (2005) The transcription factor snail induces tumor cell invasion through modulation of the epithelial cell differentiation program. Cancer Res. 65, 6237-6244. DOI
4	Iwano, M., Fischer, A., Okada, H., Plieth, D., Xue, C., Danoff, T. M. and Neilson, E. G. (2001) Conditional abatement of tissue fibrosis using nucleoside analogs to selectively corrupt DNA replication in transgenic fibroblasts. Mol. Ther. 3, 149-159. DOI
5	Otsuki, Y., Saya, H. and Arima, Y. (2018) Prospects for new lung cancer treatments that target EMT signaling. Dev. Dyn. 247, 462-472. DOI
6	Beals, C. R., Sheridan, C. M., Turck, C. W., Gardner, P. and Crabtree, G. R. (1997) Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science 275, 1930-1934. DOI
7	Bracken, C. P., Gregory, P. A., Kolesnikoff, N., Bert, A. G., Wang, J., Shannon, M. F. and Goodall, G. J. (2008) A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 68, 7846-7854. DOI
8	Chilosi, M., Poletti, V., Zamo, A., Lestani, M., Montagna, L., Piccoli, P., Pedron, S., Bertaso, M., Scarpa, A., Murer, B., Cancellieri, A., Maestro, R., Semenzato, G. and Doglioni, C. (2003) Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis. Am. J. Pathol. 162, 1495-1502. DOI
9	Kim, B. N., Ahn, D. H., Kang, N., Yeo, C. D., Kim, Y. K., Lee, K. Y., Kim, T. J., Lee, S. H., Park, M. S., Yim, H. W., Park, J. Y., Park, C. K. and Kim, S. J. (2020) TGF-beta induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci. Rep. 10, 10597. DOI
10	Mani, S. A., Yang, J., Brooks, M., Schwaninger, G., Zhou, A., Miura, N., Kutok, J. L., Hartwell, K., Richardson, A. L. and Weinberg, R. A. (2007) Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc. Natl. Acad. Sci. U.S.A. 104, 10069-10074. DOI
11	Boutet, A., Esteban, M. A., Maxwell, P. H. and Nieto, M. A. (2007) Reactivation of Snail genes in renal fibrosis and carcinomas: a process of reversed embryogenesis? Cell Cycle 6, 638-642. DOI
12	Sato, R., Semba, T., Saya, H. and Arima, Y. (2016) Concise review: stem cells and epithelial-mesenchymal transition in cancer: biological implications and therapeutic targets. Stem Cells 34, 1997-2007. DOI
13	Xie, L., Law, B. K., Chytil, A. M., Brown, K. A., Aakre, M. E. and Moses, H. L. (2004) Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia 6, 603-610. DOI
14	Zhou, B. P., Deng, J., Xia, W., Xu, J., Li, Y. M., Gunduz, M. and Hung, M. C. (2004) Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat. Cell Biol. 6, 931-940. DOI
15	Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2021) Global cancer statistics 2020: GLO-BOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209-249. DOI
16	Buckingham, M., Bajard, L., Chang, T., Daubas, P., Hadchouel, J., Meilhac, S., Montarras, D., Rocancourt, D. and Relaix, F. (2003) The formation of skeletal muscle: from somite to limb. J. Anat. 202, 59-68. DOI
17	Zhou, J. J., Meng, Z., Zhou, Y., Cheng, D., Ye, H. L., Zhou, Q. B., Deng, X. G. and Chen, R. F. (2016) Hepatitis C virus core protein regulates OCT4 expression and promotes cell cycle progression in hepatocellular carcinoma. Oncol. Rep. 36, 582-588. DOI
18	Fazilaty, H., Rago, L., Kass Youssef, K., Ocana, O. H., Garcia-Asencio, F., Arcas, A., Galceran, J. and Nieto, M. A. (2019) A gene regulatory network to control EMT programs in development and disease. Nat. Commun. 10, 5115. DOI
19	Fujita, Y., Krause, G., Scheffner, M., Zechner, D., Leddy, H. E., Behrens, J., Sommer, T. and Birchmeier, W. (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat. Cell Biol. 4, 222-231. DOI
20	Fuxe, J., Vincent, T. and Garcia de Herreros, A. (2010) Transcriptional crosstalk between TGF-beta and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes. Cell Cycle 9, 2363-2374. DOI
21	Tucker, G. C., Duband, J. L., Dufour, S. and Thiery, J. P. (1988) Cell-adhesion and substrate-adhesion molecules: their instructive roles in neural crest cell migration. Development 103 Suppl, 81-94. DOI
22	Pan, J., Fang, S., Tian, H., Zhou, C., Zhao, X., Tian, H., He, J., Shen, W., Meng, X., Jin, X. and Gong, Z. (2020) lncRNA JPX/miR-33a-5p/ Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/beta-catenin signaling. Mol. Cancer 19, 9. DOI
23	Nishitani, Y., Iwano, M., Yamaguchi, Y., Harada, K., Nakatani, K., Akai, Y., Nishino, T., Shiiki, H., Kanauchi, M., Saito, Y. and Neilson, E. G. (2005) Fibroblast-specific protein 1 is a specific prognostic marker for renal survival in patients with IgAN. Kidney Int. 68, 1078-1085. DOI
24	Okada, H., Ban, S., Nagao, S., Takahashi, H., Suzuki, H. and Neilson, E. G. (2000) Progressive renal fibrosis in murine polycystic kidney disease: an immunohistochemical observation. Kidney Int. 58, 587-597. DOI
25	Okada, H., Danoff, T. M., Kalluri, R. and Neilson, E. G. (1997) Early role of Fsp1 in epithelial-mesenchymal transformation. Am. J. Physiol. 273, F563-F574.
26	Okada, H., Strutz, F., Danoff, T. M., Kalluri, R. and Neilson, E. G. (1996) Possible mechanisms of renal fibrosis. Contrib. Nephrol. 118, 147-154. DOI
27	Oloumi, A., McPhee, T. and Dedhar, S. (2004) Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase. Biochim. Biophys. Acta 1691, 1-15. DOI
28	Pece, S. and Gutkind, J. S. (2002) E-cadherin and Hakai: signalling, remodeling or destruction? Nat. Cell Biol. 4, E72-E74. DOI
29	Perl, A. K., Wilgenbus, P., Dahl, U., Semb, H. and Christofori, G. (1998) A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392, 190-193. DOI
30	Pires, B. R., Mencalha, A. L., Ferreira, G. M., de Souza, W. F., Morgado-Diaz, J. A., Maia, A. M., Correa, S. and Abdelhay, E. S. (2017) NF-kappaB is involved in the regulation of EMT genes in breast cancer cells. PLoS ONE 12, e0169622. DOI
31	Polakis, P. (2000) Wnt signaling and cancer. Genes Dev. 14, 1837-1851. DOI
32	Arnold, S. J. and Robertson, E. J. (2009) Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat. Rev. Mol. Cell Biol. 10, 91-103. DOI
33	Bhowmick, N. A., Zent, R., Ghiassi, M., McDonnell, M. and Moses, H. L. (2001) Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. J. Biol. Chem. 276, 46707-46713. DOI
34	Wang, D., Dai, C., Li, Y. and Liu, Y. (2011) Canonical Wnt/beta-catenin signaling mediates transforming growth factor-beta1-driven podocyte injury and proteinuria. Kidney Int. 80, 1159-1169. DOI
35	Wang, J., Sridurongrit, S., Dudas, M., Thomas, P., Nagy, A., Schneider, M. D., Epstein, J. A. and Kaartinen, V. (2005) Atrioventricular cushion transformation is mediated by ALK2 in the developing mouse heart. Dev. Biol. 286, 299-310. DOI
36	Balzac, F., Avolio, M., Degani, S., Kaverina, I., Torti, M., Silengo, L., Small, J. V. and Retta, S. F. (2005) E-cadherin endocytosis regulates the activity of Rap1: a traffic light GTPase at the crossroads between cadherin and integrin function. J. Cell Sci. 118, 4765-4783. DOI
37	Barrallo-Gimeno, A. and Nieto, M. A. (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132, 3151-3161. DOI
38	Basch, M. L., Bronner-Fraser, M. and Garcia-Castro, M. I. (2006) Specification of the neural crest occurs during gastrulation and requires Pax7. Nature 441, 218-222. DOI
39	Bronner-Fraser, M. (2002) Molecular analysis of neural crest formation. J. Physiol. Paris 96, 3-8. DOI
40	Wellner, U., Schubert, J., Burk, U. C., Schmalhofer, O., Zhu, F., Sonntag, A., Waldvogel, B., Vannier, C., Darling, D., zur Hausen, A., Brunton, V. G., Morton, J., Sansom, O., Schuler, J., Stemmler, M. P., Herzberger, C., Hopt, U., Keck, T., Brabletz, S. and Brabletz, T. (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat. Cell Biol. 11, 1487-1495. DOI
41	Wu, D. and Wang, X. (2015) Application of clinical bioinformatics in lung cancer-specific biomarkers. Cancer Metastasis Rev. 34, 209-216. DOI
42	Yang, Z., Rayala, S., Nguyen, D., Vadlamudi, R. K., Chen, S. and Kumar, R. (2005) Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions. Cancer Res. 65, 3179-3184. DOI
43	Hao, J., Zhang, Y., Deng, M., Ye, R., Zhao, S., Wang, Y., Li, J. and Zhao, Z. (2014) MicroRNA control of epithelial-mesenchymal transition in cancer stem cells. Int. J. Cancer 135, 1019-1027. DOI
44	Weston, J. A. (1970) The migration and differentiation of neural crest cells. Adv. Morphog. 8, 41-114. DOI
45	Bronner, M. E. (2012) Formation and migration of neural crest cells in the vertebrate embryo. Histochem. Cell Biol. 138, 179-186. DOI
46	Carlsson, P. and Mahlapuu, M. (2002) Forkhead transcription factors: key players in development and metabolism. Dev. Biol. 250, 1-23. DOI
47	Castanon, I. and Baylies, M. K. (2002) A twist in fate: evolutionary comparison of Twist structure and function. Gene 287, 11-22. DOI
48	Chin, V. L. and Lim, C. L. (2019) Epithelial-mesenchymal plasticity-engaging stemness in an interplay of phenotypes. Stem Cell Investig. 6, 25. DOI
49	Zeisberg, M., Bonner, G., Maeshima, Y., Colorado, P., Muller, G. A., Strutz, F. and Kalluri, R. (2001) Renal fibrosis: collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation. Am. J. Pathol. 159, 1313-1321. DOI
50	Zhang, Y. and Weinberg, R. A. (2018) Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Front. Med. 12, 361-373. DOI
51	Thiery, J. P. and Sleeman, J. P. (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat. Rev. Mol. Cell Biol. 7, 131-142. DOI
52	Duband, J. L., Monier, F., Delannet, M. and Newgreen, D. (1995) Epithelium-mesenchyme transition during neural crest development. Acta Anat. (Basel) 154, 63-78. DOI
53	Eger, A., Stockinger, A., Park, J., Langkopf, E., Mikula, M., Gotzmann, J., Mikulits, W., Beug, H. and Foisner, R. (2004) beta-Catenin and TGFbeta signalling cooperate to maintain a mesenchymal phenotype after FosER-induced epithelial to mesenchymal transition. Oncogene 23, 2672-2680. DOI
54	Fan, J. M., Ng, Y. Y., Hill, P. A., Nikolic-Paterson, D. J., Mu, W., Atkins, R. C. and Lan, H. Y. (1999) Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney Int. 56, 1455-1467. DOI
55	Li, Y., Yang, J., Dai, C., Wu, C. and Liu, Y. (2003) Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J. Clin. Invest. 112, 503-516. DOI
56	Peinado, H., Olmeda, D. and Cano, A. (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat. Rev. Cancer 7, 415-428. DOI
57	Sauka-Spengler, T. and Bronner-Fraser, M. (2008) A gene regulatory network orchestrates neural crest formation. Nat. Rev. Mol. Cell Biol. 9, 557-568. DOI
58	Shih, J. Y., Tsai, M. F., Chang, T. H., Chang, Y. L., Yuan, A., Yu, C. J., Lin, S. B., Liou, G. Y., Lee, M. L., Chen, J. J., Hong, T. M., Yang, S. C., Su, J. L., Lee, Y. C. and Yang, P. C. (2005) Transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma. Clin. Cancer Res. 11, 8070-8078. DOI
59	Strutz, F., Zeisberg, M., Ziyadeh, F. N., Yang, C. Q., Kalluri, R., Muller, G. A. and Neilson, E. G. (2002) Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation. Kidney Int. 61, 1714-1728. DOI
60	Grille, S. J., Bellacosa, A., Upson, J., Klein-Szanto, A. J., van Roy, F., Lee-Kwon, W., Donowitz, M., Tsichlis, P. N. and Larue, L. (2003) The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 63, 2172-2178.
61	Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., Taite, H., Scoular, R., Miller, A. and Reeve, A. E. (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392, 402-405. DOI
62	Hartwell, K. A., Muir, B., Reinhardt, F., Carpenter, A. E., Sgroi, D. C. and Weinberg, R. A. (2006) The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc. Natl. Acad. Sci. U.S.A. 103, 18969-18974. DOI
63	Hay, E. D. (2005) The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev. Dyn. 233, 706-720. DOI
64	Hugo, H., Ackland, M. L., Blick, T., Lawrence, M. G., Clements, J. A., Williams, E. D. and Thompson, E. W. (2007) Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J. Cell. Physiol. 213, 374-383. DOI
65	Wang, G., Guo, X., Hong, W., Liu, Q., Wei, T., Lu, C., Gao, L., Ye, D., Zhou, Y., Chen, J., Wang, J., Wu, M., Liu, H. and Kang, J. (2013) Critical regulation of miR-200/ZEB2 pathway in Oct4/Sox2-induced mesenchymal-to-epithelial transition and induced pluripotent stem cell generation. Proc. Natl. Acad. Sci. U.S.A. 110, 2858-2863. DOI
66	Tepass, U., Theres, C. and Knust, E. (1990) crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 61, 787-799. DOI
67	Ungefroren, H., Witte, D. and Lehnert, H. (2018) The role of small GT-Pases of the Rho/Rac family in TGF-beta-induced EMT and cell motility in cancer. Dev. Dyn. 247, 451-461. DOI
68	De Robertis, E. M., Wessely, O., Oelgeschlager, M., Brizuela, B., Pera, E., Larrain, J., Abreu, J. and Bachiller, D. (2001) Molecular mechanisms of cell-cell signaling by the Spemann-Mangold organizer. Int. J. Dev. Biol. 45, 189-197.
69	Ezin, A. M., Fraser, S. E. and Bronner-Fraser, M. (2009) Fate map and morphogenesis of presumptive neural crest and dorsal neural tube. Dev. Biol. 330, 221-236. DOI
70	Frixen, U. H., Behrens, J., Sachs, M., Eberle, G., Voss, B., Warda, A., Lochner, D. and Birchmeier, W. (1991) E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J. Cell Biol. 113, 173-185. DOI
71	Yang, J., Mani, S. A., Donaher, J. L., Ramaswamy, S., Itzykson, R. A., Come, C., Savagner, P., Gitelman, I., Richardson, A. and Weinberg, R. A. (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117, 927-939. DOI
72	Zhang, P., Sun, Y. and Ma, L. (2015) ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle 14, 481-487. DOI
73	Gravdal, K., Halvorsen, O. J., Haukaas, S. A. and Akslen, L. A. (2007) A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clin. Cancer Res. 13, 7003-7011. DOI
74	Hodge, D. R., Hurt, E. M. and Farrar, W. L. (2005) The role of IL-6 and STAT3 in inflammation and cancer. Eur. J. Cancer 41, 2502-2512. DOI
75	Iwano, M., Plieth, D., Danoff, T. M., Xue, C., Okada, H. and Neilson, E. G. (2002) Evidence that fibroblasts derive from epithelium during tissue fibrosis. J. Clin. Invest. 110, 341-350. DOI
76	Kim, C. F., Jackson, E. L., Woolfenden, A. E., Lawrence, S., Babar, I., Vogel, S., Crowley, D., Bronson, R. T. and Jacks, T. (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121, 823-835. DOI
77	Kalluri, R. and Neilson, E. G. (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J. Clin. Invest. 112, 1776-1784. DOI
78	Karafiat, V., Dvorakova, M., Krejci, E., Kralova, J., Pajer, P., Snajdr, P., Mandikova, S., Bartunek, P., Grim, M. and Dvorak, M. (2005) Transcription factor c-Myb is involved in the regulation of the epithelial-mesenchymal transition in the avian neural crest. Cell. Mol. Life Sci. 62, 2516-2525. DOI
79	Prudkin, L., Liu, D. D., Ozburn, N. C., Sun, M., Behrens, C., Tang, X., Brown, K. C., Bekele, B. N., Moran, C. and Wistuba, I. I. (2009) Epithelial-to-mesenchymal transition in the development and progression of adenocarcinoma and squamous cell carcinoma of the lung. Mod. Pathol. 22, 668-678. DOI
80	Karafiat, V., Dvorakova, M., Pajer, P., Cermak, V. and Dvorak, M. (2007) Melanocyte fate in neural crest is triggered by Myb proteins through activation of c-kit. Cell. Mol. Life Sci. 64, 2975-2984. DOI
81	Lamouille, S., Xu, J. and Derynck, R. (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol. 15, 178-196. DOI
82	Strutz, F., Okada, H., Lo, C. W., Danoff, T., Carone, R. L., Tomaszewski, J. E. and Neilson, E. G. (1995) Identification and characterization of a fibroblast marker: FSP1. J. Cell Biol. 130, 393-405. DOI
83	Lander, R., Nordin, K. and LaBonne, C. (2011) The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1. J. Cell Biol. 194, 17-25. DOI
84	Lee, J. M., Dedhar, S., Kalluri, R. and Thompson, E. W. (2006a) The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J. Cell Biol. 172, 973-981. DOI
85	Seo, J., Ha, J., Kang, E. and Cho, S. (2021) The role of epithelial-mesenchymal transition-regulating transcription factors in anti-cancer drug resistance. Arch. Pharm. Res. 44, 281-292. DOI
86	Shaw, A. T. and Solomon, B. (2011) Targeting anaplastic lymphoma kinase in lung cancer. Clin. Cancer Res. 17, 2081-2086. DOI
87	Shin, S. Y., Rath, O., Zebisch, A., Choo, S. M., Kolch, W. and Cho, K. H. (2010) Functional roles of multiple feedback loops in extracellular signal-regulated kinase and Wnt signaling pathways that regulate epithelial-mesenchymal transition. Cancer Res. 70, 6715-6724. DOI
88	Lim, S., Becker, A., Zimmer, A., Lu, J., Buettner, R. and Kirfel, J. (2013) SNAI1-mediated epithelial-mesenchymal transition confers chemoresistance and cellular plasticity by regulating genes involved in cell death and stem cell maintenance. PLoS ONE 8, e66558. DOI
89	Leptin, M. (1999) Gastrulation in Drosophila: the logic and the cellular mechanisms. EMBO J. 18, 3187-3192. DOI
90	Leptin, M. and Affolter, M. (2004) Drosophila gastrulation: identification of a missing link. Curr. Biol. 14, R480-R482. DOI
91	Liu, Y., Lu, X., Huang, L., Wang, W., Jiang, G., Dean, K. C., Clem, B., Telang, S., Jenson, A. B., Cuatrecasas, M., Chesney, J., Darling, D. S., Postigo, A. and Dean, D. C. (2014) Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis. Nat. Commun. 5, 5660. DOI
92	Maiuthed, A., Chantarawong, W. and Chanvorachote, P. (2018) Lung cancer stem cells and cancer stem cell-targeting natural compounds. Anticancer Res. 38, 3797-3809. DOI
93	Monsoro-Burq, A. H., Wang, E. and Harland, R. (2005) Msx1 and Pax3 cooperate to mediate FGF8 and WNT signals during Xenopus neural crest induction. Dev. Cell 8, 167-178. DOI
94	Lee, T. K., Poon, R. T., Yuen, A. P., Ling, M. T., Kwok, W. K., Wang, X. H., Wong, Y. C., Guan, X. Y., Man, K., Chau, K. L. and Fan, S. T. (2006b) Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin. Cancer Res. 12, 5369-5376. DOI
95	Timmerman, L. A., Grego-Bessa, J., Raya, A., Bertran, E., Perez-Pomares, J. M., Diez, J., Aranda, S., Palomo, S., McCormick, F., Izpisua-Belmonte, J. C. and de la Pompa, J. L. (2004) Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 18, 99-115. DOI
96	Tepass, U. (1996) Crumbs, a component of the apical membrane, is required for zonula adherens formation in primary epithelia of Drosophila. Dev. Biol. 177, 217-225. DOI
97	Teschendorff, A. E., Journee, M., Absil, P. A., Sepulchre, R. and Caldas, C. (2007) Elucidating the altered transcriptional programs in breast cancer using independent component analysis. PLoS Comput. Biol. 3, e161. DOI
98	Thiery, J. P., Acloque, H., Huang, R. Y. and Nieto, M. A. (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890. DOI
99	Valcourt, U., Kowanetz, M., Niimi, H., Heldin, C. H. and Moustakas, A. (2005) TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol. Biol. Cell 16, 1987-2002. DOI