Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2014

Open Access 01-12-2014 | Review

Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention

Authors: Samantha Kaufhold, Benjamin Bonavida

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2014

Login to get access

Abstract

Snail1 is the founding member of the Snail superfamily of zinc-finger transcription factors, which also includes Snail2 (Slug) and Snail3 (Smuc). The superfamily is involved in cell differentiation and survival, two processes central in cancer research. Encoded by the SNAI1 gene located on human chromosome 20q13.2, Snail1 is composed of 264 amino acids and usually acts as a transcriptional repressor. Phosphorylation and nuclear localization of Snail1, governed by PI3K and Wnt signaling pathways crosstalk, are critical in Snail1’s regulation. Snail1 has a pivotal role in the regulation of epithelial-mesenchymal transition (EMT), the process by which epithelial cells acquire a migratory, mesenchymal phenotype, as a result of its repression of E-cadherin. Snail1-induced EMT involves the loss of E-cadherin and claudins with concomitant upregulation of vimentin and fibronectin, among other biomarkers. While essential to normal developmental processes such as gastrulation, EMT is associated with metastasis, the cancer stem cell phenotype, and the regulation of chemo and immune resistance in cancer. Snail1 expression is a common sign of poor prognosis in metastatic cancer, and tumors with elevated Snail1 expression are disproportionately difficult to eradicate by current therapeutic treatments. The significance of Snail1 as a prognostic indicator, its involvement in the regulation of EMT and metastasis, and its roles in both drug and immune resistance point out that Snail1 is an attractive target for tumor growth inhibition and a target for sensitization to cytotoxic drugs.
Appendix
Available only for authorised users
Literature
1.
Nieto MA: The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 2002, 3: 155-166.PubMedCrossRef
2.
Boulay J, Dennefeld C, Alberga A: The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers. Nature. 1987, 330: 395-398.PubMedCrossRef
3.
Manzanares M, Locascio A, Nieto MA: The increasing complexity of the snail gene superfamily in metazoan evolution. Trends Genet. 2001, 17: 178-181.PubMedCrossRef
4.
Grau Y, Carteret C, Simpson P: Mutations and chromosomal rearrangements affecting the expression of snail, a gene involved in embryonic patterning in Drosophila melanogaster. Genetics. 1984, 108: 347-360.PubMedCentralPubMed
5.
Nusslein-Volhard C, Weischaus E, Kluding H: Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster. I. Zygotic loci on the second chromosome. Wilheim Roux’s Arch Dev Biol. 1984, 193: 267-282.CrossRef
6.
Twigg S, Wilkie AOM: Characterization of the human snail (SNAI1) gene and exclusion as a major disease gene in craniosynostosis. Hum Genet. 1999, 105: 320-326.PubMed
7.
Paznekas W, Okajima K, Schertzer M, Wood S, Jabs E: Genomic organization, expression, and chromosome location of the human snail gene (SNAI1) and a related processed pseudogene (SNAI1P). Genomics. 1999, 62: 42-49.PubMedCrossRef
8.
Barrallo-Gimeno A, Nieto MA: Evolutionary history of the snail/scratch superfamily. Trends Genet. 2009, 25: 248-252.PubMedCrossRef
9.
Human Snail1: sequence retrieved from and alignments run through NIH BLAST http://​blast.​st-va.​ncbi.​nlm.​nih.​gov/​Blast.​cgi.​,http://www.uniprot.org/uniprot/O95863
10.
11.
Carver EA, Jiang R, Gridley T: The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol. 2001, 21: 8184-8188.PubMedCentralPubMedCrossRef
12.
Barrallo-Gimeno A, Nieto MA: The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development. 2005, 132: 3151-3161.PubMedCrossRef
13.
Kajita M, McClinic K, Wade P: Aberrant expression of the transcription factors Snail and Slug alters the response to genotoxic stress. Mol Cell Biol. 2004, 24: 7559-7566.PubMedCentralPubMedCrossRef
14.
Mani S, Guo W, Liao MJ, Eaton E, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133: 704-715.PubMedCentralPubMedCrossRef
15.
Zhou W, Lv R, Qi W, Wu D, Xu Y, Liu W, Mou Y, Wang L: Snail contributes to the maintenance of stem cell-like phenotype cells in human pancreatic cancer. PLoS One. 2014, 9: e87409-PubMedCentralPubMedCrossRef
16.
Wang H, Zhang G, Zhang H, Zhang F, Zhou BP, Ning F, Wang HS, Cai SH, Du J: Acquisition of epithelial-mesenchymal transition phenotype and cancer stem cell-like properties in cisplatin-resistant lung cancer cells through AKT/β-catenin/Snail signaling pathway. Eur J Pharmacol. 2014, 723: 156-166.PubMedCrossRef
17.
18.
Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, Nieto MA, Cano A, Portillo F: A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. EMBO J. 2005, 24: 3446-3458.PubMedCentralPubMedCrossRef
19.
Zhu GH, Huang C, Feng ZZ, Lv XH, Qiu ZJ: Hypoxia-induced snail expression through transcriptional regulation by HIF-1alpha in pancreatic cancer cells. Dig Dis Sci. 2013, 58: 3503-3515.PubMedCrossRef
20.
Barbera MJ, Puig I, Dominguez D, Julien-Grille S, Guaita-Esteruelas S, Peiro S, Baulida J, Franci C, Dedhar S, Larue L, Garcia de Herreros A: Regulation of snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene. 2004, 23: 7345-7354.PubMedCrossRef
21.
Brandl M, Seidler B, Haller F, Adamski J, Schmid RM, Saur D, Schneider G: IKKalpha controls canonical TGFBeta-SMAD signaling to regulate genes expressing snail and slug during EMT in Panc1 cells. J Cell Sci. 2010, 123: 4231-4239.PubMedCrossRef
22.
Thuault S, Tan EJ, Peinado H, Cano A, Heldin CH, Moustakas A: HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem. 2008, 283: 33437-33446.PubMedCentralPubMedCrossRef
23.
McPhee T, McDonald P, Oloumi A, Dedhar S: Integrin-linked kinase regulates E-Cadherin expression through PARP-1. Dev Dyn. 2008, 237: 2737-2747.PubMedCrossRef
24.
Yadav A, Kumar B, Datta J, Teknos T, Kumar P: IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res. 2011, 9: 1658-1667.PubMedCentralPubMedCrossRef
25.
Zhang XH, Liang X, Wang TS, Liang XH, Zuo RJ, Deng WB, Zhang ZR, Qin FN, Zhao ZA, Yang ZM: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) induction on Snail expression during mouse decidualization. Mol Cell Endocrinol. 2013, 381: 272-279.PubMedCrossRef
26.
Li X, Deng W, Lobo-Ruppert S, Ruppert J: Gli1 acts through Snail and E-Cadherin to promote nuclear signaling by Beta-catenin. Oncogene. 2007, 26: 4489-4498.PubMedCentralPubMedCrossRef
27.
Fujita N, Jaye D, Kajita M, Geigerman C, Moreno C, Wade P: MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell. 2003, 113: 207-219.PubMedCrossRef
28.
Dhasarathy A, Kajita M, Wade P: The transcription factor snail mediates epithelial to mesenchymal transitions by repression of estrogen receptor-alpha. Mol Endocrinol. 2007, 21: 2907-2918.PubMedCentralPubMedCrossRef
29.
Grotegut S, von Schweinitz D, Christofori G, Lehembre F: Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail. EMBO J. 2006, 25: 3534-3545.PubMedCentralPubMedCrossRef
30.
Palmer M, Majumder P, Cooper J, Yoon H, Wade P, Boss J: Yin Yang 1 regulates the expression of Snail through a distal enhancer. Mol Cancer Res. 2009, 7: 221-229.PubMedCentralPubMedCrossRef
31.
Peiro S, Escriva M, Puig I, Barbera MJ, Dave N, Herranz N, Larriba MJ, Takkunen M, Franci C, Munoz A, Virtanen I, Baulida J, Garcia de herreros A: Snail1 transcriptional repressor binds to its own promoter and controls its expression. Nucleic Acids Res. 2006, 34: 2077-2084.PubMedCentralPubMedCrossRef
32.
Kim NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, Cha SY, Ryu JK, Yoon D, Fearon ER, Rowe RG, Lee S, Maher CA, Weiss SJ, Yook JI: A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesencymal transition. J Cell Biol. 2011, 195: 417-433.PubMedCentralPubMedCrossRef
33.
Zhou BP, Deng J, Xia W, Xu J, Li Y, Gunduz M, Hung MC: Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 2004, 6: 931-940.PubMedCrossRef
34.
Katoh M, Katoh M: Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades. Cancer Biol Ther. 2006, 5: 1059-1064.PubMedCrossRef
35.
Vinas-Castells R, Beltran M, Valls G, Gomez I, Garcia JM, Montserrat-Sentis B, Baulida J, Bonilla F, Garcia de herreros A, Diaz VM: The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation. J Biol Chem. 2010, 285: 3794-3805.PubMedCentralPubMedCrossRef
36.
Yang Z, Rayala S, Nguyen D, Vadlmudi R, Chen S, Kumar R: Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchhyme transition, modulates snail’s subcellular localization and functions. Cancer Res. 2005, 65: 3179-3184.PubMed
37.
Dominguez D, Montserrat-Sentis B, Virgos-Soler A, Guaita S, Grueso J, Porta M, Puig I, Baulida J, Franci C, Garcia de Herreros A: Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor. Mol Cell Biol. 2003, 23: 5078-5089.PubMedCentralPubMedCrossRef
38.
Ko H, Kim H, Kim N, Lee S, Kim K, Hong S, Yook J: Nuclear localization signals of the E-Cadherin transcriptional repressor Snail. Cells Tissues Organs. 2007, 185: 66-72.PubMedCrossRef
39.
Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP: Stabilization of snail by NFkappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 2009, 15: 416-428.PubMedCentralPubMedCrossRef
40.
41.
Yook JI, Li XY, Ota I, Fearon ER, Weiss SJ: Wnt-dependent regulation of the E-cadherin repressor snail. J Biol Chem. 2005, 280: 11740-11748.PubMedCrossRef
42.
Zhang JP, Zeng C, Xu L, Gong J, Fang JH, Zhuang SM: MicroRNA-148a suppresses the epithelial-mesenchymal transition and metastasis of hepatoma cells by targeting Met/Snail signaling.Oncogene 2013, Epub ahead of print.,
43.
Tsubaki M, Komai M, Fujimoto SI, Itoh T, Imano M, Sakamoto K, Shimaoka H, Takeda T, Ogawa N, Mashimo K, Fujiwara D, Mukai J, Sakaguchi K, Satou T, Nishida S: Activation of NF-κB by the RANKL/RANK system up-regulates snail and twist expressions and induces epithelial-to-mesenchymal transition in mammary tumor cell lines. J Exp Clin Cancer Res. 2013, 32: 62-PubMedCentralPubMedCrossRef
44.
Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, van Roy F, Dargemont C, de Herreros AG, Bellacosa A, Larue L: Activation of NF-κB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene. 2007, 26: 7445-7456.PubMedCrossRef
45.
Cheng JC, Chang HM, Leung P: TGF-Beta1 inhibits trophoblast cell invasion by inducing snail-mediated down-regulation of ve-cadherin. J Biol Chem. 2013, 288: 33181-33192.PubMedCentralPubMedCrossRef
46.
Horiguchi K, Shirakihara T, Nakano A, Imamura T, Miyazono K, Saitoh M: Role of Ras signaling in the induction of snail by transforming growth factor-beta. J Biol Chem. 2009, 284: 245-253.PubMedCrossRef
47.
48.
Jiang GM, Wang HS, Zhang F, Zhang KS, Liu ZC, Fang R, Wang H, Cai SH, Du J: Histone deacetylase inhibitor induction of epithelial-mesenchymal transitions via up-regulation of Snail facilitates cancer progression. Biochim Biophys Acta. 1833, 2013: 663-671.
49.
Takeichi M: Functional correlation between cell adhesive properties and some cell surface proteins. J Cell Biol. 1977, 75: 464-474.PubMedCrossRef
50.
Berx G, Staes K, van Hengel J, Molemans F, Bussemakers M, von Bokhoven A, van Roy F: Cloning and characterization of the human invasion suppressor gene E-cadherin (CDH1). Genomics. 1995, 26: 281-289.PubMedCrossRef
51.
Van Roy F, Berx G: The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008, 65: 3756-3788.PubMedCrossRef
52.
Takeichi M, Matsunami H, Inoue T, Kimura Y, Suzuki S, Tanaka T: Roles of cadherins in patterning of the developing brain. Dev Neurosci. 1997, 19: 86-87.PubMedCrossRef
53.
54.
Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA: The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000, 2: 76-83.PubMedCrossRef
55.
Larue L, Ohsugi M, Hirchenhain J, Kemler R: E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci U S A. 1994, 91: 8263-8267.PubMedCentralPubMedCrossRef
56.
Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou P, Evers B, Zhou B: G9a interacts with snail and is critical for snail-mediated E-cadherin repression in human breast cancer. J Clin Investig. 2012, 122: 1469-1486.PubMedCentralPubMedCrossRef
57.
Hou Z, Peng H, Ayyanathan K, Yan KP, Langer EM, Longmore GD, Rauscher FJ: The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression. Mol Cell Biol. 2008, 28: 3198-3207.PubMedCentralPubMedCrossRef
58.
Shi Y, Whetstine JR: Dynamic regulation of histone lysine methylation by demethylases. Mol Cell. 2007, 25: 1-14.PubMedCrossRef
59.
Peinado H, Ballestar E, Esteller M, Cano A: Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol Cell Biol. 2004, 24: 306-319.PubMedCentralPubMedCrossRef
60.
Lin Y, Wu Y, Li J, Dong C, Ye X, Chi YI, Evers BM, Zhou BP: The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1. EMBO J. 2010, 29: 1803-1816.PubMedCentralPubMedCrossRef
61.
Dong C, Wu Y, Wang Y, Wang C, Kang T, Rychahou PG, Chi YI, Evers BM, Zhou BP: Interaction with Suv39H1 is critical for Snail-mediated E-cadherin repression in breast cancer. Oncogene. 2013, 32: 1351-1362.PubMedCentralPubMedCrossRef
62.
Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, Fee F, Katsanakis KD, Rose DW, Mischak H, Sedivy JM, Kolch W: Suppression of Raf-1 kinase activity and MAP kinase signaling by RKIP. Nature. 1999, 401: 173-177.PubMedCrossRef
63.
Yeung K, Rose DW, Dhillon AS, Yaros D, Gusafsson M, Chatterjee D, McFerran B, Wyche J, Kolch W, Sedivy JM: Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation. Mol Cell Biol. 2001, 21: 7201-7217.CrossRef
64.
Chatterjee D, Bai Y, Wang Z, Beach S, Mott S, Roy R, Braastad C, Sun Y, Mukhopadhyay A, Aggarwal BB, Darnowski J, Pantazis P, Wyche J, Fu Z, Kitagwa Y, Keller ET, Sedivy JM, Yeung KC: RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem. 2004, 279: 17515-17523.PubMedCrossRef
65.
Park S, Yeung ML, Beach S, Shields JM, Yeung KC: RKIP downregulates B-Raf kinase activity in melanoma cancer cells. Oncogene. 2005, 24: 3535-3540.PubMedCrossRef
66.
Al-Mulla F, Hagan S, Behbehani AI, Bitar MS, George SS, Going JJ, Garcia JJ, Scott L, Fyfe N, Murray GI, Kolch W: Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients. J Clin Oncol. 2006, 24: 5672-5679.PubMedCrossRef
67.
Fu Z, Kitagawa Y, Shen R, Shah R, Mehra R, Rhodes D, Keller PJ, Mizokami A, Dunn R, Chinnaiyan AM, Yao Z, Keller ET: Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. Prostate. 2005, 66: 248-256.CrossRef
68.
Beach S, Tang H, Park S, Dhillon AS, Keller ET, Kolch W, Yeung KC: Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene. 2008, 27: 2243-2248.PubMedCentralPubMedCrossRef
69.
Vazquez F, Devreotes P: Regulation of PTEN Function as a PIP3 Gatekeeper through Membrane. Cell Cycle. 2006, 5: 1523-1527.PubMedCrossRef
70.
Escriva M, Peiro S, Herranz H, Villagrasa P, Dave N, Montserrat-Sentis B, Murray SA, Franci C, Gridley T, Virtanen I, Garcia de herreros A: Repression of PTEN Phosphatase by Snail1 Transcriptional Factor during Gamma Radiation-Induced Apoptosis. Mol Cell Biol. 2008, 28: 1528-1540.PubMedCentralPubMedCrossRef
71.
Stambolic V, MacPherson D, Sas D, Lin Y, Snow B, Jang Y, Benchimol S, Mak TW: Regulation of PTEN transcription by p53. Mol Cell. 2001, 8: 317-325.PubMedCrossRef
72.
Yamada KM, Araki M: Tumor suppressor PTEN: modulator of cell signalling, growth, migration and apoptosis. J Cell Sci. 2002, 114: 2375-2382.
73.
Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S: Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993, 123: 1777-1788.PubMedCrossRef
74.
Ando-Akatsuka Y, Saitou M, Hirase T, Kishi M, Sakakibara A, Itoh M, Yonemura S, Furuse M, Tsukita S: Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues. J Cell Biol. 1996, 133: 43-47.PubMedCrossRef
75.
Ikenouchi J, Matsuda M, Furuse M, Tsukita S: Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci. 2003, 116: 1959-1967.PubMedCrossRef
76.
77.
Martinez-Estrada O, Culleres A, Vilaro S: The transcription factors Slug and Snail act as repressors of Claudin-1 expression in epithelial cells. Biochem J. 2006, 394: 449-457.PubMedCentralPubMedCrossRef
78.
Martin T, Jiang W: Loss of tight junction barrier function and its role in cancer metastasis. BBA Biomembranes. 2009, 1788: 872-891.PubMedCrossRef
79.
Zaretsky J, Barnea I, Aylon Y, Gorivodsky M, Wreschner D, Keydar I: MUC1 gene overexpressed in breast cancer: structure and transcriptional activity of the MUC1 promoter and role of estrogen receptor alpha (ERalpha) in regulation of the MUC1 gene expression. Mol Cancer. 2006, 5: 57-PubMedCentralPubMedCrossRef
80.
81.
Hollingsworth M, Swanson B: Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004, 4: 45-60.PubMedCrossRef
82.
83.
Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J: Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. J Biol Chem. 2002, 277: 39209-39216.PubMedCrossRef
84.
Sanchez-Tillo E, Lazaro A, Torrent R, Cuatrecasas M, Vaquero EC, Castells A, Engel P, Postigo A: ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene. 2010, 29: 3490-3500.PubMedCrossRef
85.
86.
Lilienbaum A, Paulin D: Activation of the human vimentin gene by the Tax human T-cell leukemia virus. I. Mechanisms of regulation by the NF-kappa B transcription factor. J Biol Chem. 1993, 268: 2180-2188.PubMed
87.
Wu Y, Zhang X, Salmon M, Lin X, Zehner ZE: TGFbeta1 regulation of vimentin gene expression during differentiation of the C2C12 skeletal myogenic cell line requires Smads, AP-1 and Sp1 family members. Biochim Biophys Acta. 2007, 1773: 427-439.PubMedCentralPubMedCrossRef
88.
Zhu QS, Rosenblatt K, Huang KL, Lahat G, Brobey R, Bolshakov S, Nguyen T, Ding Z, Belousov R, Bill K, Luo X, Lazar A, Dicker A, Mills GB, Hung MC, Lev D: Vimentin is a novel AKT1 target mediating motility and invasion. Oncogene. 2011, 30: 457-470.PubMedCentralPubMedCrossRef
89.
Gilles C, Polette M, Mestdagt M, Nawrocki-Raby B, Ruggeri P, Birembaut P, Foidart JM: Transactivation of vimentin by beta-catenin in human breast cancer cells. Cancer Res. 2003, 63: 2658-2664.PubMed
90.
Lang SH, Hyde C, Reid IN, Hitchcock IS, Hart CA, Bryden AA, Villette JM, Stower MJ, Maitland NJ: Enhanced expression of vimentin in motile prostate cell lines and in poorly differentiated and metastatic prostate carcinoma. Prostate. 2002, 52: 253-263.PubMedCrossRef
91.
Zhao Y, Yan Q, Long X, Chen X, Wang Y: Vimentin affects the mobility and invasiveness of prostate cancer cells. Cell Biochem Funct. 2008, 26: 571-577.PubMedCrossRef
92.
Hynes RO, Yamada KM: Fibronectins: multifunctional modular glycoproteins. J Cell Biol. 1982, 95: 369-377.PubMedCrossRef
93.
Mosher DF: Fibronectin. 1989, Academic Press, Inc., San Diego
94.
95.
Benecky MJ, Kolvenback CG, Amrani DL, Mosesson MN: Evidence that binding to the carboxyl-terminal heparin-binding domain (HepII) dominates the interaction between plasma fibronectin and heparin. Biochem. 1988, 27: 7565-7571.CrossRef
96.
97.
Mostafavi-Pour Z, Askari JA, Whittard JD, Humphries MJ: Identification of a novel heparin-binding site in the alternatively spliced IIICS region of fibronectin: roles of integrins and proteoglycans in cell adhesion to fibronectin splice variants. Matrix Biol. 2001, 20: 63-73.PubMedCrossRef
98.
Liao YF, Gotwals PJ, Koteliansky VE, Sheppard D, Van De Water L: The EIIIA segment of fibronectin is a ligand for integrins α9β1 andα 4β1 providing a novel mechanism for regulating cell adhesion by alternative splicing. J Biol Chem. 2002, 277: 14467-14474.PubMedCrossRef
99.
Erat MC, Sladek B, Campbell ID, Vakonakis I: Structural analysis of collagen type I interactions with human fibronectin reveals a cooperative binding mode. J Biol Chem. 2013, 288: 17441-17450.PubMedCentralPubMedCrossRef
100.
George EL, Georges-Labouesse EN, Patel-King RS, Rayburn H, Hynes RO: Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development. 1993, 119: 1079-1091.PubMed
101.
Moll R, Franke WW, Schiller DL, Geiger B, Krepler R: The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982, 31: 11-24.PubMedCrossRef
102.
Fuchs E, Cleveland DW: A structural scaffolding of intermediate filaments in health and disease. Science. 1998, 279: 514-519.PubMedCrossRef
103.
Coulombe PA, Omary MB: ‘Hard‘ and ‘soft‘ principles defining the structure, function and regulation of keratin intermediate filaments. Curr Opin Cell Biol. 2002, 14: 110-122.PubMedCrossRef
104.
Galarneau L, Loranger A, Gilbert S, Marceau N: Keratins modulate hepatic cell adhesion, size and G1/S transition. Exp Cell Res. 2007, 313: 179-194.PubMedCrossRef
105.
Oshima RG, Baribault H, Caulín C: Oncogenic regulation and function of keratins 8 and 18. Cancer Metastasis Rev. 1996, 15: 445-471.PubMedCrossRef
106.
Lin MH, Liu SY, Su HJ, Liu YC: Functional role of matrix metalloproteinase 28 in the oral squamous cell carcinoma. Oral Oncol. 2006, 42: 907-913.PubMedCrossRef
107.
Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA: Matrix Metalloproteinases: a review. Crit Rev Oral Biol Med. 1993, 4: 197-250.PubMed
108.
Senior RM, Griffin GL, Fliszar CJ, Shapiro SD, Goldberg GI, Welgus HG: Human 92- and 72- kilodalton type IV collagenases are elastases. J Biol Chem. 1991, 266: 7870-7875.PubMed
109.
Seltzer JL, Adams SA, Grant GA, Eisen AZ: Purification and properties of a gelatin-specific neutral protease from human skin. J Biol Chem. 1981, 256: 4662-4668.PubMed
110.
Seltzer JL, Eisen AZ, Bauer EA, Morris NP, Glanville RW, Burgeson RE: Cleavage of type VII collagen by interstitial collagenase and type IV collagenase (Gelatinase) derived from human skin. J Biol Chem. 1989, 264: 3822-3826.PubMed
111.
Gadher SJ, Schmid TM, Heck LW, Woolley DE: Cleavage of collagen type X by human synovial collagenase and neutrophil elastase. Matrix. 1989, 9: 109-115.PubMedCrossRef
112.
Huhtala P, Tuuttila A, Chow LT, Lohi J, Keski-Oja J, Tryggvason K: Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells. J Biol Chem. 1991, 266: 16485-16490.PubMed
113.
Qiao B, Johnson N, Gao J: Epithelial-mesenchymal transition in oral squamous cell carcinoma triggered by transforming growth factor-β1 is Snail family-dependent and correlates with matrix metalloproteinase-2 and -9 expressions. Int J Oncol. 2010, 37: 663-668.PubMed
114.
Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S: Metastatic potential correlates with enzymic degradation of basement membrane collagen. Nature. 1980, 284: 67-68.PubMedCrossRef
115.
Garbisa S, Pozzati R, Muschel RJ, Saffiotti U, Ballin M, Goldfarb RH, Khoury G, Liotta LA: Secretion of type IV collagenolytic protease and metastatic phenotype: induction by transfection with C-Ha-ras but not C-Ha-ras plus Ad2-Ela. Cancer Res. 1987, 47: 1523-1528.PubMed
116.
Nakajima M, Welch DR, Belloni PN, Nicholson GL: Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res. 1987, 47: 4869-4876.PubMed
117.
Bernhard EJ, Muschel RJ, Hughes EN: Mr 92,000 gelatinase release correlates with the metastatic phenotype in transformed rat embryo cells. Cancer Res. 1990, 50: 3872-3877.PubMed
118.
Mahabir R, Tanino M, Elmansuri A, Wang L, Kimura T, Itoh T, Ohba Y, Nishihara H, Shirato H, Tsuda M, Tanaka S: Sustained elevation of Snail promotes glial-mesenchymal transition after irradiation in malignant glioma. Neuro Oncol. 2013, 0: 1-15.
119.
Porfiri E, Rubinfeld B, Albert I, Hovanes K, Waterman M, Polakis P: Induction of a β-catenin-LEF-1 complex by wnt-1 and transforming mutants of β-catenin. Oncogene. 1997, 15: 2833-2839.PubMedCrossRef
120.
Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P: Stabilization of β-catenin by genetic defects in melanoma cell lines. Science. 1997, 275: 1790-1792.PubMedCrossRef
121.
Jamora C, DasGupta R, Kocieniewski P, Fuchs E: Links between signal transduction, transcription and adhesion in epithelial bud development. Nature. 2003, 422: 317-322.PubMedCentralPubMedCrossRef
122.
Kim K, Lu Z, Hay ED: Direct evidence for a role of betacatenin/LEF-1 signalling pathway in the induction of EMT. Cell Biol Int. 2002, 26: 463-476.PubMedCrossRef
123.
Waterman ML: Lymphoid enhancer factor/T cell factor expression in colorectal cancer. Cancer Metastasis Rev. 2004, 23: 41-52.PubMedCrossRef
124.
Medici D, Hay E, Goodenough D: Cooperation between Snail and LEF-1 transcription factors is essential for TGF-β1-induced epithelial-mesenchymal transition. Mol Biol Cell. 2006, 17: 1871-1879.PubMedCentralPubMedCrossRef
125.
De Craene B, van Roy F, Berx G: Unraveling signaling cascades for the Snail family of transcription factors. Cell Signal. 2005, 17: 535-547.PubMedCrossRef
126.
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience with long-term follow-up. Histopathology. 1991, 19: 403-410.PubMedCrossRef
127.
Dieterich M, Goodman SN, Rojas-Corona RR, Emralino AB, Jimenez-Joseph D, Sherman ME: Multivariate analysis of prognostic features in malignant pleural effusions from breast cancer patients. Acta Cytol. 1994, 38: 945-952.PubMed
128.
Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, Nieto MA: Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene. 2002, 21: 3241-3246.PubMedCrossRef
129.
Elloul S, Bukholt Elstrand M, Nesland JM, Trope CG, Kvalheim G, Goldberg I, Reich R, Davidson B: Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer. 2005, 103: 1631-1643.PubMedCrossRef
130.
Jiao W, Miyazaki K, Kitajima Y: Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo. Br J Cancer. 2002, 86: 98-101.PubMedCentralPubMedCrossRef
131.
Miyoshi A, Kitajima Y, Miyazaki K: Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma. Br J Cancer. 2005, 92: 252-258.PubMedCentralPubMed
132.
Woo HY, Min AL, Choi JY, Bae SH, Yoon SK, Jung CK: Clinicopathologic significance of the expression of Snail in hepatocellular carcinoma. Korean J Hepatol. 2011, 17: 12-18.PubMedCentralPubMedCrossRef
133.
Elloul S, Silins I, Trope CG, Benshushan A, Davidson B, Reich R: Expression of E-cadherin transcriptional regulators in ovarian carcinoma. Virchows Arch. 2006, 449: 520-528.PubMedCrossRef
134.
Rosiavitz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Hofler H, Becker KF: Differential expression of the epithelial-mesenchymal transition regulators Snail, SIP1, and Twist in gastric cancer. Am J Pathol. 2002, 161: 1881-1891.CrossRef
135.
Shin NR, Jeong EH, Choi CI, Moon HJ, Kwon CH, Chu IS, Kim GH, Jeon TY, Kim DH, Lee JH, Park do Y: Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer. BMC Cancer. 2012, 12: 521-PubMedCentralPubMedCrossRef
136.
Yokoyama K, Kamata N, Hayashi E, Hoteiya T, Ueda N, Fujimoto R, Nagayama M: Reverse correlation of E-cadherin and snail expression in oral squamous cell carcinoma cells in vitro. Oral Oncol. 2001, 37: 65-71.PubMedCrossRef
137.
Hotz B, Arndt M, Dullat S, Bhargava S, Buhr HJ, Hotz HG: Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer. Clin Cancer Res. 2007, 13: 4769-4776.PubMedCrossRef
138.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59: 225-249.PubMedCrossRef
139.
Roy H, Smyrk T, Koetsier J, Victor T, Wali R: The transcriptional repressor SNAIL is overexpressed in human colon cancer. Dig Dis Sci. 2005, 50: 42-46.PubMedCrossRef
140.
Fan F, Samuel S, Evans KW, Lu J, Xia L, Zhou Y, Sceusi E, Tozzi F, Ye XC, Mani SA, Ellis LM: Overexpression of Snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells. Cancer Med. 2012, 1: 5-16.PubMedCentralPubMedCrossRef
141.
Yu Q, Zhang K, Wang X, Liu X, Zhang Z: Expression of transcription factors snail, slug, and twist in human bladder carcinoma. J Exp Clin Cancer Res. 2010, 29: 119-PubMedCentralPubMedCrossRef
142.
Bruyere F, Namdarian B, Corcoran NM, Pedersen J, Ockrim J, Voelzke BB, Mete U, Costello AJ, Hovens CM: Snail expression is an independent predictor of tumor recurrence in superficial bladder cancers. Urol Oncol. 2010, 28: 591-596.PubMedCrossRef
143.
Poser I, Dominguez D, Garcia de Herreros A, Varnai A, Buettner R, Bosserhoff AK: Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem. 2001, 276: 24661-24666.PubMedCrossRef
144.
Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y: Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell. 2009, 15: 195-206.PubMedCrossRef
145.
Saito T, Oda Y, Tsuneyoshi M: E-cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features. Am J Pathol. 2001, 159: 2117-2124.PubMedCentralPubMedCrossRef
146.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90.PubMedCrossRef
147.
Delahunt B, Miller RJ, Srigley JR, Evans AJ, Samaratunga H: Gleason grading: past, present and future. Histopathology. 2012, 60: 75-86.PubMedCrossRef
148.
149.
Edwards IJ: Proteoglycans in prostate cancer. Nat Rev Urol. 2012, 21: 196-206.CrossRef
150.
151.
Nackaerts K, Verbeken E, Deneffe G, Vanderschueren B, Demedts M, David G: Heparan sulfate proteoglycan expression in human lung-cancer cells. Int J Cancer. 1997, 74: 335-345.PubMedCrossRef
152.
Poblete C, Fulla J, Gallardo M, Munoz V, Castellon EA, Gallegos I, Contreras HR: Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer. Int J Oncol. 2014, 44: 647-654.PubMedCentralPubMed
153.
Chen Z, Li S, Huang K, Zhang Q, Wang J, Li X, Hu T, Wang S, Yang R, Jia Y, Sun H, Tang F, Zhou H, Shen J, Ma D, Wang S: The nuclear protein expression levels of SNAI1 and ZEB1 are involved in the progression and lymph node metastasis of cervical cancer via the epithelial-mesenchymal transition pathway. Hum Pathol. 2013, 44: 2097-2105.PubMedCrossRef
154.
Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414: 105-111.PubMedCrossRef
155.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003, 100: 3983-3988.PubMedCentralPubMedCrossRef
156.
Jones RJ, Matsui WH, Smith BD: Cancer stem cells: are we missing the target?. J Natl Cancer Inst. 2004, 96: 583-585.PubMedCrossRef
157.
Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006, 126: 663-676.PubMedCrossRef
158.
Moon JH, Heo JS, Kim JS, Jun EK, Lee JH, Kim A, Kim J, Kim J, Whang KY, Kang YK, Yeo S, Lim HJ, Han DW, Kim DW, Oh S, Yoon BS, Schöler HR, You S: Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1. Cell Res. 2011, 21: 1305-1315.PubMedCentralPubMedCrossRef
159.
Moon JH, Yun W, Kim J, Hyeon S, Kang PJ, Park G, Kim A, Oh S, Whang KY, Kim DW, Yoon BS, You S: Reprogramming of mouse fibroblasts into induced pluripotent stem cells with Nanog. Biochem Biophys Res Commun. 2013, 431: 444-449.PubMedCrossRef
160.
Zhu L, Qin H, Li PY, Xu SN, Pang HF, Zhao HZ, Li DM, Zhao Q: Response gene to complement-32 enhances metastatic phenotype by mediating transforming growth factor beta-induced epithelial-mesenchymal transition in human pancreatic cancer cell line BxPC-3. J Exp Clin Cancer Res. 2012, 31: 29-PubMedCentralPubMedCrossRef
161.
Huang J, Song H, Liu B, Yu B, Wang R, Chen L: Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma. J Exp Clin Cancer Res. 2013, 32: 84-PubMedCentralPubMedCrossRef
162.
Fujii R, Imanishi Y, Shibata K, Sakai N, Sakamoto K, Shigetomi S, Habu N, Otsuka K, Sato Y, Watanabe Y, Ozawa H, Tomita T, Kameyama K, Fujii M, Ogawa K: Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma. J Exp Clin Cancer Res. 2014, 33: 40-PubMedCentralPubMedCrossRef
163.
Zhuo W, Wang Y, Zhuo X, Zhang Y, Ao X, Chen Z: Knockdown of Snail, a novel zinc finger transcription factor, via RNA interference increases A549 cell sensitivity to cisplatin via JNK/mitochondrial pathway. Lung Cancer. 2008, 62: 8-14.PubMedCrossRef
164.
Hsu DS, Lan HY, Huang CH, Tai SK, Chang SY, Tsai TL, Chang CC, Tzeng CH, Wu KJ, Kao JY, Yang MH: Regulation of excision repair cross-complementation group 1 by Snail contributes to cisplatin resistance in head and neck cancer. Clin Cancer Res. 2010, 16: 4561-4571.PubMedCrossRef
165.
Haslehurst AM, Koti M, Dharsee M, Nuin P, Evans K, Geraci J, Childs T, Chen J, Li J, Weberpals J, Davey S, Squire J, Park PC, Feilotter H: EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer. 2012, 12: 91-PubMedCentralPubMedCrossRef
166.
Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, Bapat SA: Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells. 2009, 27: 2059-2068.PubMedCrossRef
167.
Yin T, Wang C, Liu T, Zhao G, Zha Y, Yang M: Expression of Snail in pancreatic cancer promotes metastasis and chemoresistance. J Surg Res. 2007, 141: 196-203.PubMedCrossRef
168.
Vega S, Morales AV, Ocana OH, Valdes F, Fabregat I, Nieto MA: Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 2004, 18: 1131-1141.PubMedCentralPubMedCrossRef
169.
Baritaki S, Yeung K, Palladino M, Berenson J, Bonavida B: Pivotal roles of snail inhibition and RKIP induction by the proteasome inhibitor NPI-0052 in tumor cell chemoimmunosensitization. Cancer Res. 2009, 69: 8376-8385.PubMedCrossRef
170.
Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B: Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin's lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer Res. 2005, 65: 264-276.PubMed
171.
Vega MI, Baritaki S, Huerta-Yepez S, Martinez-Paniagua MA, Bonavida B: A potential mechanism of rituximab-induced inhibition of tumorgrowth through its sensitization to tumor necrosis factor-related apoptosis-inducing ligand-expressing host cytotoxic cells. Leuk Lymphoma. 2011, 52: 108-121.PubMedCrossRef
172.
Akalay I, Janji B, Hasmim M, Noman MZ, Thiery JP, Mami-Chouaib F, Chouaib S: EMT impairs breast carcinoma cell susceptibility to CTL-mediated lysis through autophagy induction. Autophagy. 2013, 9: 1104-1106.PubMedCentralPubMedCrossRef
173.
Akalay I, Janji B, Hasmim M, Noman MZ, André F, De Cremoux P, Bertheau P, Badoual C, Vielh P, Larsen AK, Sabbah M, Tan TZ, Keira JH, Hung NT, Thiery JP, Mami-Chouaib F, Chouaib S: Epithelial-to mesenchymal transition and autophagy induction in breast carcinoma promote escape from T-cell-mediated lysis. Cancer Res. 2013, 73: 2418-2427.PubMedCrossRef
174.
Lee SH, Lee SJ, Chung JY, Jung YS, Choi SY, Hwang SH, Choi D, Ha NC, Park BJ: p53, secreted by K-Ras-Snail pathway, is endocytosed by K-Ras-mutated cells; implication of target-specific drug delivery and early diagnostic marker. Oncogene. 2009, 28: 2005-2014.PubMedCrossRef
175.
Lee SH, Shen GN, Jung YS, Lee SJ, Chung JY, Kim HS, Xu Y, Choi Y, Lee JW, Ha NC, Song GY, Park BJ: Antitumor effect of novel small chemical inhibitors of Snail-p53 binding in K-Ras-mutated cancer cells. Oncogene. 2010, 29: 4576-4587.PubMedCrossRef
176.
177.
Javaid S, Zhang J, Anderssen E, Black JC, Wittner BS, Tajima K, Ting DT, Smolen GA, Zubrowski M, Desai R, Maheswaran S, Ramaswamy S, Whetstine JR, Haber DA: Dynamic chromatin modification sustains epithelial-mesenchymal transition following inducible expression of Snail-1. Cell Rep. 2013, 5: 1679-1689.PubMedCentralPubMedCrossRef
178.
Shah P, Gau Y, Sabnis G: Histone deacetylase inhibitor entinostat reverses epithelial to mesenchymal transition of breast cancer cells by reversing the repression of E-cadherin. Breast Cancer Res Treat. 2014, 143: 99-111.PubMedCrossRef
179.
Hatzivassiliou G, Haling JF, Chen H, Song K, Price S, Heald R, Hewitt JF, Zak M, Peck A, Orr C, Merchant M, Hoeflich KP, Chan J, Luoh SM, Anderson DJ, Ludlam MJ, Wiesmann C, Ultsch M, Friedman LS, Malek S, Belvin M: Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature. 2013, 501: 232-236.PubMedCrossRef
180.
Miller C, Oliver K, Farley J: MEK1/2 inhibitors in the treatment of gynecologic malignancies. Gynecol Oncol. 2014, 133: 128-137.PubMedCrossRef
181.
McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, Cervello M, Libra M, Candido S, Malaponte G, Mazzarino MC, Fagone P, Nicoletti F, Bäsecke J, Mijatovic S, Maksimovic-Ivanic D, Milella M, Tafuri A, Chiarini F, Evangelisti C, Cocco L, Martelli AM: Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance. Oncotarget. 2012, 3: 1068-1111.PubMedCentralPubMedCrossRef
182.
NIH Database.. .,http://​clinicaltrials.​gov
183.
Mimasu S, Sengoku T, Fukuzawa S, Umehara T, Yokoyama S: Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25Å. Biochem Biophys Res Commun. 2008, 366: 15-22.PubMedCrossRef
184.
Pubchem Database.. [],http://​pubchem.​ncbi.​nlm.​nih.​gov/​summary/​summary.​cgi?​cid=​444732&​loc=​ec_​rcs
185.
Pubchem Database.. [],http://​pubchem.​ncbi.​nlm.​nih.​gov/​summary/​summary.​cgi?​cid=​4688&​loc=​ec_​rcs
186.
Pubchem Database.. [],http://​pubchem.​ncbi.​nlm.​nih.​gov/​summary/​summary.​cgi?​cid=​6918837
187.
Pubchem Database.. [],http://​pubchem.​ncbi.​nlm.​nih.​gov/​summary/​summary.​cgi?​cid=​4261
Metadata
Title
Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention
Authors
Samantha Kaufhold
Benjamin Bonavida
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2014
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-014-0062-0

Other articles of this Issue 1/2014

Journal of Experimental & Clinical Cancer Research 1/2014 Go to the issue

Research

CK2α, over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells

Research

Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas

Review

Immunologic treatments for precancerous lesions and uterine cervical cancer

Research

Parthenolide induces apoptosis via TNFRSF10B and PMAIP1 pathways in human lung cancer cells

Research

Efficacy and safety of ipilimumab in elderly patients with pretreated advanced melanoma treated at Italian centres through the expanded access programme

Research

Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits