Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis

Misiakos, 2011, Current treatment for colorectal liver metastases, World J. Gastroenterol., 17, 4067, 10.3748/wjg.v17.i36.4067

Drewes, 2016, Sporadic colorectal cancer: Microbial contributors to disease prevention, development and therapy, Br. J. Cancer, 115, 273, 10.1038/bjc.2016.189

Kinzler, 1996, Lessons from hereditary colorectal cancer, Cell, 87, 159, 10.1016/S0092-8674(00)81333-1

Shook, 2003, Mechanisms, mechanics and function of epithelial to mesenchymal transitions in early development, Mech. Dev., 120, 1351, 10.1016/j.mod.2003.06.005

Kalluri, 2009, EMT: When epithelial cells decide to become mesenchymal-like cells, J. Clin. Investig., 119, 1417, 10.1172/JCI39675

Kang, 2004, Epithelial to mesenchymal transitions: Twist in development and metastasis, Cell, 118, 277, 10.1016/j.cell.2004.07.011

Singh, 2010, EMT, cancer stem cells and drug resistance: An emerging axis of evil in the war on cancer, Oncogene, 29, 4741, 10.1038/onc.2010.215

Spaderna, 2006, A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer, Gastroenterology, 131, 830, 10.1053/j.gastro.2006.06.016

Thiery, 2009, Epithelial-mesenchymal transitions in development and disease, Cell, 139, 871, 10.1016/j.cell.2009.11.007

Tsai, 2013, Epithelial to mesenchymal plasticity in carcinoma metastasis, Genes Dev., 27, 2192, 10.1101/gad.225334.113

Cano, 2000, The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression, Nat. Cell Biol., 2, 76, 10.1038/35000025

Graff, 1995, E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas, Cancer Res., 55, 5195

Palacios, 2005, Lysosomal targeting of E-cadherin: A unique mechanism for the down-regulation of cell-cell adhesion during epithelial to mesenchymal transitions, Mol. Cell Biol., 25, 389, 10.1128/MCB.25.1.389-402.2005

Yun, 2014, Loss of E-Cadherin expression is associated with a poor prognosis in stage III colorectal cancer, Oncology, 86, 318, 10.1159/000360794

Saito, 2008, Clinical significance of fibronectin expression in colorectal cancer, Mol. Med. Rep., 1, 77

Yi, 2016, High expression of fibronectin is associated with poor prognosis, cell proliferation and malignancy via the NF-kappaB/p53-apoptosis signaling pathway in colorectal cancer, Oncol. Rep., 36, 3145, 10.3892/or.2016.5177

Yan, 2015, N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer, Mol. Med. Rep., 12, 2999, 10.3892/mmr.2015.3687

Francí, C., Gallén, M., Alameda, F., Baró, T., Iglesias, M., Virtanen, I., and de Herreros, A.G. (2009). Snail1 protein in the stroma as a new putative prognosis marker for colon tumours. PLoS ONE, 4.

Shioiri, 2006, Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients, Br. J. Cancer, 94, 1816, 10.1038/sj.bjc.6603193

Gomez, I., Peña, C., Herrera, M., Muñoz, C., Larriba, M.J., Garcia, V., Dominguez, G., Silva, J., Rodriguez, R., and de Herreros, A. (2011). TWIST1 is expressed in colorectal carcinomas and predicts patient survival. PLoS ONE, 6.

Yu, 2013, Twist2 is a valuable prognostic biomarker for colorectal cancer, World J. Gastroenterol., 19, 2404, 10.3748/wjg.v19.i15.2404

Zhang, 2013, High expression of ZEB1 correlates with liver metastasis and poor prognosis in colorectal cancer, Oncol. Lett., 5, 564, 10.3892/ol.2012.1026

Kahlert, 2011, Overexpression of ZEB2 at the invasion front of colorectal cancer is an independent prognostic marker and regulates tumor invasion in vitro, Clin. Cancer Res., 17, 7654, 10.1158/1078-0432.CCR-10-2816

Skog, 2011, Expression and prognostic value of transcription factor PROX1 in colorectal cancer, Br. J. Cancer, 105, 1346, 10.1038/bjc.2011.297

Li, 2015, Overexpression of forkhead Box C2 promotes tumor metastasis and indicates poor prognosis in colon cancer via regulating epithelial-mesenchymal transition, Am. J. Cancer Res., 5, 2022

Weng, 2016, FOXM1 and FOXQ1 are promising prognostic biomarkers and novel targets of tumor-suppressive miR-342 in human colorectal cancer, Clin. Cancer Res., 22, 4947, 10.1158/1078-0432.CCR-16-0360

Li, 2015, Contribution of FOXC1 to the progression and metastasis and prognosis of human colon cancer, J. Clin. Oncol., 33, 636, 10.1200/jco.2015.33.3_suppl.636

Chu, 2012, FOXM1 expression correlates with tumor invasion and a poor prognosis of colorectal cancer, Acta Histochem., 114, 755, 10.1016/j.acthis.2012.01.002

Nieto, 2005, The Snail genes as inducers of cell movement and survival: Implications in development and cancer, Development, 132, 3151, 10.1242/dev.01907

Peinado, 2004, Snail mediates E-cadherin repression by the recruitment of the sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex, Mol. Cell. Biol., 24, 306, 10.1128/MCB.24.1.306-319.2004

Herranz, 2008, Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor, Mol. Cell. Biol., 28, 4772, 10.1128/MCB.00323-08

Tong, 2012, EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin, Oncogene, 31, 583, 10.1038/onc.2011.254

Lin, 2010, Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial to mesenchymal transition, Oncogene, 29, 4896, 10.1038/onc.2010.234

Dong, 2012, G9a interacts with SNAIL and is critical for SNAIL-mediated E-cadherin repression in human breast cancer, J. Clin. Investig., 122, 1469, 10.1172/JCI57349

Dong, 2013, Interaction with Suv39H1 is critical for SNAIL-mediated E-cadherin repression in breast cancer, Oncogene, 32, 1351, 10.1038/onc.2012.169

Thuault, 2008, HMGA2 and Smads coregulate SNAIL1 expression during induction of epithelial toto-mesenchymal transition, J. Biol. Chem., 283, 33437, 10.1074/jbc.M802016200

Smit, 2009, A Twist-SNAIL axis critical for TrkB-induced epithelial to mesenchymal transition-like transformation, anoikis resistance, and metastasis, Mol. Cell. Biol., 29, 3722, 10.1128/MCB.01164-08

Guaita, 2002, SNAIL induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression, J. Biol. Chem., 277, 39209, 10.1074/jbc.M206400200

Stemmer, 2008, Snail promotes WNT target gene expression and interacts with β-catenin, Oncogene, 27, 5075, 10.1038/onc.2008.140

Saad, 2010, Notch mediated epithelial to mesenchymal transformation is associated with increased expression of the SNAIL transcription factor, Int. J. Biochem. Cell Biol., 42, 1115, 10.1016/j.biocel.2010.03.016

Liu, 2014, SNAIL regulates Nanog status during the epithelial to mesenchymal transition via the Smad1/AKT/GSK3beta signaling pathway in non-small-cell lung cancer, Oncotarget, 5, 3880, 10.18632/oncotarget.2006

Yang, 2015, WNT signaling through SNAIL1 and Zeb1 regulates bone metastasis in lung cancer, Am. J. Cancer Res., 5, 748

Larriba, 2004, The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer, Nat. Med., 10, 917, 10.1038/nm1095

Hwang, 2011, SNAIL regulates interleukin-8 expression, stem cell-like activity, and tumorigenicity of human colorectal carcinoma cells, Gastroenterology, 141, 279, 10.1053/j.gastro.2011.04.008

Yang, 2004, Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis, Cell, 117, 927, 10.1016/j.cell.2004.06.006

Yang, 2012, SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities, EMBO J., 31, 110, 10.1038/emboj.2011.364

Torres, 2016, Twist1-induced activation of human fibroblasts promotes matrix stiffness by upregulating palladin and collagen alpha1(VI), Oncogene, 35, 5224, 10.1038/onc.2016.57

Celesti, 2013, Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors, Gastroenterology, 145, 647, 10.1053/j.gastro.2013.05.011

Helbling, 2015, TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer, Oncotarget, 6, 874, 10.18632/oncotarget.2716

Postigo, 1999, ZEB represses transcription through interaction with the corepressor CtBP, Proc. Natl. Acad. Sci. USA, 96, 6683, 10.1073/pnas.96.12.6683

Torrent, 2010, ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1, Oncogene, 29, 3490, 10.1038/onc.2010.102

Postigo, 2003, Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins, EMBO J., 22, 2453, 10.1093/emboj/cdg226

Wang, 2007, Opposing LSD1 complexes function in developmental gene activation and repression programmes, Nature, 446, 882, 10.1038/nature05671

Aigner, 2007, The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity, Oncogene, 26, 6979, 10.1038/sj.onc.1210508

Spaderna, 2008, The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer, Cancer Res., 68, 537, 10.1158/0008-5472.CAN-07-5682

Siles, 2013, ZEB1 promotes invasiveness of colorectal carcinoma cells through the opposing regulation of uPA and PAI-1, Clin. Cancer Res., 19, 1071, 10.1158/1078-0432.CCR-12-2675

Petrova, 2008, Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype, Cancer Cell, 13, 407, 10.1016/j.ccr.2008.02.020

Lu, 2012, Prospero homeobox 1 promotes epithelial-mesenchymal transition in colon cancer cells by inhibiting E-cadherin via miR-9, Clin. Cancer Res., 18, 6416, 10.1158/1078-0432.CCR-12-0832

Kaneda, 2010, FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth, Cancer Res., 70, 2053, 10.1158/0008-5472.CAN-09-2161

Zhang, 2011, Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis, Cancer Res., 71, 1292, 10.1158/0008-5472.CAN-10-2825

Abba, 2013, Unraveling the role of FOXQ1 in colorectal cancer metastasis, Mol. Cancer Res., 11, 1017, 10.1158/1541-7786.MCR-13-0024

Wierstra, 2013, FOXM1 (Forkhead box M1) in tumorigenesis: Overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy, Adv. Cancer Res., 119, 191, 10.1016/B978-0-12-407190-2.00016-2

Yang, 2013, FOXM1 promotes the epithelial to mesenchymal transition by stimulating the transcription of Slug in human breast cancer, Cancer Lett., 340, 104, 10.1016/j.canlet.2013.07.004

Zhang, 2016, A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer, Oncogene, 36, 807, 10.1038/onc.2016.249

Mohri, 1997, Prognostic significance of E-cadherin expression in human colorectal cancer tissue, Surg. Today, 27, 606, 10.1007/BF02388215

He, X., Chen, Z., Jia, M., and Zhao, X. (2013). Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: Evidence from meta-analysis. PLoS ONE, 8.

Roberts, 2003, The two faces of transforming growth factor beta in carcinogenesis, Proc. Natl. Acad. Sci. USA, 100, 8621, 10.1073/pnas.1633291100

Pohl, 2010, SMAD4 mediates mesenchymal-epithelial reversion in SW480 colon carcinoma cells, Anticancer Res., 30, 2603

Zhao, 2008, Inhibition of STAT3 Tyr705 phosphorylation by SMAD4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells, Cancer Res., 68, 4221, 10.1158/0008-5472.CAN-07-5123

Voorneveld, 2014, Loss of SMAD4 alters BMP signaling to promote colorectal cancer cell metastasis via activation of Rho and ROCK, Gastroenterology, 147, 196, 10.1053/j.gastro.2014.03.052

Labelle, 2011, Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis, Cancer Cell, 20, 576, 10.1016/j.ccr.2011.09.009

Brabletz, 2001, Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment, Proc. Natl. Acad. Sci. USA, 98, 10356, 10.1073/pnas.171610498

Yook, 2005, WNT-dependent regulation of the E-cadherin repressor snail, J. Biol. Chem., 280, 11740, 10.1074/jbc.M413878200

Wu, 2012, Canonical WNT signaling regulates Slug activity and links epithelial-mesenchymal transition with epigenetic Breast Cancer 1, Early Onset (BRCA1) repression, Proc. Natl. Acad. Sci. USA, 109, 16654, 10.1073/pnas.1205822109

Qi, 2014, WNT3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression, J. Exp. Clin. Cancer Res., 33, 107, 10.1186/s13046-014-0107-4

Gujral, 2014, A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal transition and metastasis, Cell, 159, 844, 10.1016/j.cell.2014.10.032

Lee, 2015, IWR-1 inhibits epithelial-mesenchymal transition of colorectal cancer cells through suppressing WNT/beta-catenin signaling as well as survivin expression, Oncotarget, 6, 27146, 10.18632/oncotarget.4354

Huang, 2014, TMPRSS4 correlates with colorectal cancer pathological stage and regulates cell proliferation and self-renewal ability, Cancer Biol. Ther., 15, 297, 10.4161/cbt.27308

Jung, 2008, TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition, Oncogene, 27, 2635, 10.1038/sj.onc.1210914

Maschler, 2005, Tumor cell invasiveness correlates with changes in integrin expression and localization, Oncogene, 24, 2032, 10.1038/sj.onc.1208423

Larzabal, 2014, TMPRSS4 regulates levels of integrin α5 in NSCLC through miR-205 activity to promote metastasis, Br. J. Cancer, 4, 764, 10.1038/bjc.2013.761

Calvo, 2015, TMPRSS4: An emerging potential therapeutic target in cancer, Br. J. Cancer, 112, 4, 10.1038/bjc.2014.403

Kim, 2010, TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways, Carcinogenesis, 31, 597, 10.1093/carcin/bgq024

Kang, 2013, Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors, Bioorg. Med. Chem. Lett., 23, 1748, 10.1016/j.bmcl.2013.01.055

Zhu, 2011, FMNL2 is a positive regulator of cell motility and metastasis in colorectal carcinoma, J. Pathol., 224, 377, 10.1002/path.2871

Li, 2010, FMNL2 enhances invasion of colorectal carcinoma by inducing epithelial-mesenchymal transition, Mol. Cancer Res., 8, 1579, 10.1158/1541-7786.MCR-10-0081

Ren, 2016, MicroRNA-206 functions as a tumor suppressor in colorectal cancer by targeting FMNL2, J. Cancer Res. Clin. Oncol., 142, 581, 10.1007/s00432-015-2053-8

Li, 2016, MicroRNA-613 targets FMNL2 and suppresses progression of colorectal cancer, Am. J. Transl. Res., 8, 5475

Lu, 2015, MicroRNA-34a targets FMNL2 and E2F5 and suppresses the progression of colorectal cancer, Exp. Mol. Pathol., 99, 173, 10.1016/j.yexmp.2015.06.014

Liang, 2013, MicroRNA-137, an HMGA1 target, suppresses colorectal cancer cell invasion and metastasis in mice by directly targeting FMNL2, Gastroenterology, 144, 624, 10.1053/j.gastro.2012.11.033

Jenkins, 2001, Human eIF5A2 on chromosome 3q25–q27 is a phylogenetically conserved vertebrate variant of eukaryotic translation initiation factor 5A with tissue-specific expression, Genomics, 71, 101, 10.1006/geno.2000.6418

Bao, 2015, Eukaryotic translation initiation factor 5A2 (eIF5A2) regulates chemoresistance in colorectal cancer through epithelial mesenchymal transition, Cancer Cell Int., 15, 109, 10.1186/s12935-015-0250-9

Zhu, 2012, Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition, Gut, 61, 562, 10.1136/gutjnl-2011-300207

Uchiyama, 2015, The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis, Cancer Med., 4, 1558, 10.1002/cam4.502

Mehta, 2014, A prospective study of macrophage inhibitory cytokine-1 (MIC-1/GDF15) and risk of colorectal cancer, J. Natl. Cancer Inst., 106, dju016, 10.1093/jnci/dju016

Wallin, 2011, Growth differentiation factor 15: A prognostic marker for recurrence in colorectal cancer, Br. J. Cancer, 104, 1619, 10.1038/bjc.2011.112

Mehta, 2015, Association between plasma levels of macrophage inhibitory Cytokine-1 before diagnosis of colorectal cancer and mortality, Gastroenterology, 149, 614, 10.1053/j.gastro.2015.05.038

Li, 2016, GDF15 promotes EMT and metastasis in colorectal cancer, Oncotarget, 7, 860, 10.18632/oncotarget.6205

Baba, 2010, HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers, Am. J. Pathol., 176, 2292, 10.2353/ajpath.2010.090972

Zhang, W., Shi, X., Peng, Y., Wu, M., Zhang, P., Xie, R., Wu, Y., Yan, Q., Liu, S., and Wang, J. (2015). HIF-1alpha promotes epithelial-mesenchymal transition and metastasis through direct regulation of ZEB1 in colorectal cancer. PLoS ONE, 10.

Santoyo-Ramos, P., Likhatcheva, M., Garcia-Zepeda, E.A., Castaneda-Patlan, M.C., and Robles-Flores, M. (2014). Hypoxia-inducible factors modulate the stemness and malignancy of colon cancer cells by playing opposite roles in canonical WNT signaling. PLoS ONE, 9.

Kim, 2015, Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer, World J. Gastroenterol., 21, 9887, 10.3748/wjg.v21.i34.9887

Gossett, 1989, A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes, Mol. Cell. Biol., 9, 5022

Potthoff, 2007, MEF2: A central regulator of diverse developmental programs, Development, 134, 4131, 10.1242/dev.008367

Kinsey, 2002, MEF2: A calcium-dependent regulator of cell division, differentiation and death, Trends Biochem. Sci., 27, 40, 10.1016/S0968-0004(01)02031-X

Su, 2016, MEF2D transduces microenvironment stimuli to ZEB1 to promote epithelial-mesenchymal transition and metastasis in colorectal cancer, Cancer Res., 76, 5054, 10.1158/0008-5472.CAN-16-0246

Wang, 2017, NUBPL, a novel metastasis-related gene, promotes colorectal carcinoma cell motility by inducing epithelial-mesenchymal transition, Cancer Sci., 108, 1169, 10.1111/cas.13243

Grandclement, C., Pallandre, J.R., Valmary Degano, S., Viel, E., Bouard, A., Balland, J., Remy-Martin, J.P., Simon, B., Rouleau, A., and Boireau, W. (2011). Neuropilin-2 expression promotes TGF-beta1-mediated epithelial to mesenchymal transition in colorectal cancer cells. PLoS ONE, 6.

Gemmill, 2017, The neuropilin 2 isoform NRP2b uniquely supports TGFbeta-mediated progression in lung cancer, Sci. Signal., 10, eaag0528, 10.1126/scisignal.aag0528

Horak, P., Tomasich, E., Vanhara, P., Kratochvilova, K., Anees, M., Marhold, M., Lemberger, C.E., Gerschpacher, M., Horvat, R., and Sibilia, M. (2014). TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo. Sci. Rep., 4.

Jiang, 2016, TUSC3 suppresses glioblastoma development by inhibiting Akt signaling, Tumour Biol., 37, 12039, 10.1007/s13277-016-5072-4

Kratochvilova, 2015, Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells, Int. J. Cancer, 137, 1330, 10.1002/ijc.29502

Yachida, 2010, Distant metastasis occurs late during the genetic evolution of pancreatic cancer, Nature, 467, 1114, 10.1038/nature09515

Levy, 1999, High-density screen of human tumor cell lines for homozygous deletions of loci on chromosome arm 8p, Genes Chromosomes Cancer, 24, 42, 10.1002/(SICI)1098-2264(199901)24:1<42::AID-GCC6>3.0.CO;2-F

Takanishi, 1997, Chromosome 8 Losses in Colorectal Carcinoma: Localization and Correlation With Invasive Disease, J. Mol. Diagn., 2, 3, 10.1016/S1084-8592(97)80003-3

Gu, 2016, TUSC3 promotes colorectal cancer progression and epithelial-mesenchymal transition (EMT) through WNT/β-catenin and MAPK signalling, J. Pathol., 239, 60, 10.1002/path.4697

Halder, 2006, Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis, Cancer Res., 66, 6156, 10.1158/0008-5472.CAN-05-3261

Anumanthan, 2006, Oncogenic serine-threonine kinase receptor-associated protein modulates the function of Ewing sarcoma protein through a novel mechanism, Cancer Res., 66, 10824, 10.1158/0008-5472.CAN-06-1599

Matsuda, 2000, Molecular cloning and characterization of human MAWD, a novel protein containing WD-40 repeats frequently overexpressed in breast cancer, Cancer Res., 60, 13

Li, 2001, WD-repeat proteins: Structure characteristics, biological function, and their involvement in human diseases, Cell. Mol. Life Sci., 58, 2085, 10.1007/PL00000838

Datta, 1998, Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling, J. Biol. Chem., 273, 34671, 10.1074/jbc.273.52.34671

Kashikar, 2010, Serine threonine receptor-associated protein (STRAP) plays a role in the maintenance of mesenchymal morphology, Cell Signal., 22, 138, 10.1016/j.cellsig.2009.09.024

Yuan, 2016, Novel role of STRAP in progression and metastasis of colorectal cancer through WNT/beta-catenin signaling, Oncotarget, 7, 16023, 10.18632/oncotarget.7532

Chi, 2016, MicroRNAs in colorectal carcinoma—From pathogenesis to therapy, J. Exp. Clin. Cancer Res., 35, 43, 10.1186/s13046-016-0320-4

Hur, 2013, MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis, Gut, 62, 1315, 10.1136/gutjnl-2011-301846

Korpal, 2008, The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2, J. Biol. Chem., 283, 14910, 10.1074/jbc.C800074200

Park, 2008, The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2, Genes Dev., 22, 894, 10.1101/gad.1640608

Davalos, 2012, Dynamic epigenetic regulation of the MicroRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis, Oncogene, 31, 2062, 10.1038/onc.2011.383

Chen, 2012, miR-200c inhibits invasion and migration in human colon cancer cells SW480/620 by targeting ZEB1, Clin. Exp. Metastasis, 29, 457, 10.1007/s10585-012-9463-7

Sun, 2014, MiR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma, Mol. Cell. Biochem., 390, 19, 10.1007/s11010-013-1950-x

Zheng, 2014, MiR-132 inhibits colorectal cancer invasion and metastasis via directly targeting ZEB2, World J. Gastroenterol., 20, 6515, 10.3748/wjg.v20.i21.6515

Geng, 2014, MicroRNA-192 suppresses liver metastasis of colon cancer, Oncogene, 33, 5332, 10.1038/onc.2013.478

Sun, 2014, MicroRNA-335 inhibits invasion and metastasis of colorectal cancer by targeting ZEB2, Med. Oncol., 31, 982, 10.1007/s12032-014-0982-8

Hahn, 2013, SNAIL and miR-34a feed-forward regulation of ZNF281/ZBP99 promotes epithelial-mesenchymal transition, EMBO J., 32, 3079, 10.1038/emboj.2013.236

Rokavec, 2014, IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis, J. Clin. Investig., 124, 1853, 10.1172/JCI73531

Siemens, 2011, MiR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions, Cell Cycle, 10, 4256, 10.4161/cc.10.24.18552

Long, 2013, Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2, J. Transl. Med., 11, 275, 10.1186/1479-5876-11-275

Meng, 2013, Genetic and epigenetic down-regulation of microRNA-212 promotes colorectal tumor metastasis via dysregulation of MnSOD, Gastroenterology, 145, 426, 10.1053/j.gastro.2013.04.004

Zhao, 2014, MiR-30b regulates migration and invasion of human colorectal cancer via SIX1, Biochem. J., 460, 117, 10.1042/BJ20131535

Zhao, 2014, MiR-320a suppresses colorectal cancer progression by targeting Rac1, Carcinogenesis, 35, 886, 10.1093/carcin/bgt378

Chen, 2017, MiR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT, Exp. Cell Res., 352, 104, 10.1016/j.yexcr.2017.01.022

Zhao, 2017, MiR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGFβ-mediated epithelial to mesenchymal transition, Mol. Cancer, 16, 12, 10.1186/s12943-017-0585-z

Costa, 2017, MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells, Oncotarget, 8, 24292, 10.18632/oncotarget.14464

Wang, 2014, MiR-29b suppresses tumor growth and metastasis in colorectal cancer via downregulating Tiam1 expression and inhibiting epithelial-mesenchymal transition, Cell Death Dis., 5, e1335, 10.1038/cddis.2014.304

Hu, 2016, MiR-363-3p inhibits the epithelial-to-mesenchymal transition and suppresses metastasis in colorectal cancer by targeting Sox4, Biochem. Biophys. Res. Commun., 474, 35, 10.1016/j.bbrc.2016.04.055

Xi, 2016, MicroRNA-17 induces epithelial-mesenchymal transition consistent with the cancer stem cell phenotype by regulating CYP7B1 expression in colon cancer, Int. J. Mol. Med., 38, 499, 10.3892/ijmm.2016.2624

Li, 2016, MiR-139-5p inhibits the epithelial-mesenchymal transition and enhances the chemotherapeutic sensitivity of colorectal cancer cells by downregulating BCL2, Sci. Rep., 6, 27157, 10.1038/srep27157

Cui, 2016, MiR-375 inhibits the invasion and metastasis of colorectal cancer via targeting SP1 and regulating EMT-associated genes, Oncol. Rep., 36, 487, 10.3892/or.2016.4834

Zhang, 2016, MiR-497 suppresses epithelial-mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1, Onco Targets Ther., 9, 6597, 10.2147/OTT.S114609

Ferraro, 2014, Epigenetic regulation of mir-21 in colorectal cancer: Itgb4 as a novel mir-21 target and a three-gene network (mir-21-itgbeta4-pdcd4) as predictor of metastatic tumor potential, Epigenetics, 9, 129, 10.4161/epi.26842

Liang, 2015, The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer, Oncotarget, 6, 22513, 10.18632/oncotarget.4154

Guo, 2014, BRAF-activated long non-coding RNA contributes to colorectal cancer migration by inducing epithelial-mesenchymal transition, Oncol. Lett., 8, 869, 10.3892/ol.2014.2154

Wu, 2014, Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer, Oncol. Rep., 32, 395, 10.3892/or.2014.3186

Yue, 2016, LncRNA-ATB mediated E-cadherin repression promotes the progression of colon cancer and predicts poor prognosis, J. Gastroenterol. Hepatol., 31, 595, 10.1111/jgh.13206

Han, 2016, Long non-coding RNA AFAP1-AS1 facilitates tumor growth and promotes metastasis in colorectal cancer, Biol. Res., 49, 36, 10.1186/s40659-016-0094-3

Wang, 2016, Long non-coding RNA TUG1 promotes colorectal cancer metastasis via EMT pathway, Oncotarget, 7, 51713, 10.18632/oncotarget.10563

Shen, 2017, Long non-coding RNA SPRY4-IT1 pormotes colorectal cancer metastasis by regulate epithelial-mesenchymal transition, Oncotarget, 8, 14479, 10.18632/oncotarget.10407

Lu, 2017, The high expression of long non-coding RNA PANDAR indicates a poor prognosis for colorectal cancer and promotes metastasis by EMT pathway, J. Cancer Res. Clin. Oncol., 143, 71, 10.1007/s00432-016-2252-y

Han, 2017, MiR-429 mediates tumor growth and metastasis in colorectal cancer, Am. J. Cancer Res., 7, 218

Cai, 2017, MicroRNA-194 modulates epithelial-mesenchymal transition in human colorectal cancer metastasis, Onco Targets Ther., 10, 1269, 10.2147/OTT.S125172

Guo, 2016, WNT/β-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling, Oncotarget, 7, 42513, 10.18632/oncotarget.9893

Tang, 2014, MicroRNA-29a promotes colorectal cancer metastasis by regulating matrix metalloproteinase 2 and E-cadherin via KLF4al, Br. J. Cancer, 110, 450, 10.1038/bjc.2013.724

Gupta, 2006, Cancer metastasis: Building a framework, Cell, 127, 679, 10.1016/j.cell.2006.11.001

Lim, 2014, Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer, J. Clin. Pathol., 67, 848, 10.1136/jclinpath-2014-202499

Acloque, 2009, Epithelial-mesenchymal transitions: The importance of changing cell state in development and disease, J. Clin. Investig., 119, 1438, 10.1172/JCI38019

Pantel, 2004, Dissecting the metastatic cascade, Nat. Rev. Cancer, 4, 448, 10.1038/nrc1370

Steinert, 2014, Immune escape and survival mechanisms in circulating tumor cells of colorectal cancer, Cancer Res., 74, 1694, 10.1158/0008-5472.CAN-13-1885

Cohen, 2008, Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer, J. Clin. Oncol., 26, 3213, 10.1200/JCO.2007.15.8923

Cohen, 2009, Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer, Ann. Oncol., 20, 1223, 10.1093/annonc/mdn786

Satelli, 2015, Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression, Clin. Cancer Res., 21, 899, 10.1158/1078-0432.CCR-14-0894

Yokobori, 2013, Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis, Cancer Res., 73, 2059, 10.1158/0008-5472.CAN-12-0326

Gorges, 2012, Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition, BMC Cancer, 12, 2407, 10.1186/1471-2407-12-178