Breast cancer progression: controversies and consensus in the molecular mechanisms of metastasis and EMT
Breast cancer progression: controversies and consensus in the molecular mechanisms of metastasis and EMT. Rabbit Polyclonal to MYL7 by increased microenvironmental rigidity, and was not recapitulated by expression of an E-cad mutant lacking its extracellular domain name. Twist expression, but not that of Snail, reinitiated metastatic outgrowth in dormant Orlistat D2.OR cells. Our findings show that EMT and its down-regulated expression of E-cad circumvent breast cancer dormancy in part by facilitating 1 integrin expression necessary for metastatic outgrowth. INTRODUCTION Dissemination of tumor cells from the primary lesion is the most common event in the metastatic process and leads to the shedding of millions of carcinoma cells into the circulation each day (Yoshida test, where a p value < 0.05 was considered significant. Values of p for all those experiments analyzed are indicated. Supplementary Material [Supplemental Materials] Click here to view. Acknowledgments We thank Pfizer for generously providing the small molecule inhibitors against FAK and Pyk2. Orlistat W.P.S. was supported in part by grants from the National Institutes of Health ("type":"entrez-nucleotide","attrs":"text":"CA129359","term_id":"35011154","term_text":"CA129359"CA129359), the Susan G. Komen for Orlistat the Remedy Foundation (BCTR0706967), and the Department of Defense (“type”:”entrez-nucleotide”,”attrs”:”text”:”BC084561″,”term_id”:”54038369″,”term_text”:”BC084561″BC084561). M.K.W. was supported by a fellowship from the American Cancer Society (PF-09120-01). Abbreviations used: 2Dtwo-dimensional3Dthree-dimensionalCMVcytomegalovirusE-cadepithelial cadherinEGFepidermal growth factorEGFRepidermal growth factor receptorEMTepithelial-mesenchymal transitionERK1/2extracellular signal-regulated kinase 1/2FAKfocal adhesionGFPgreen fluorescent proteinHANhyperplastic alveolar noduleMECmammary epithelial cellNM-ENMuMG cells transformed by EGFRRTKreceptor tyrosine kinaseTGF-transforming growth factor-TRITGF- receptor type IVSVGvesicular stomatitis virus-glycoproteinWTwild-type Footnotes This article was published online ahead of print in MBoC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E11-04-0306) on May 25, 2011. Recommendations Ansieau S, et al. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell. 2008;14:79C89. [PubMed] [Google Scholar]Aslakson CJ, Miller FR. 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