Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: implications for tumor progression

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• dc.contributor.author Wanami, Luke S.
• dc.contributor.author Chen, Hsin-Ying
• dc.contributor.author Peir, Sandóra
• dc.contributor.author García de Herreros, Antonio
• dc.contributor.author Bachelder, Robin E.
• dc.date.accessioned 2019-01-24T08:51:55Z
• dc.date.available 2019-01-24T08:51:55Z
• dc.date.issued 2008
• dc.description.abstract The E-cadherin transcriptional repressor Snail is a prognostic marker for metastatic breast carcinoma, as well as a critical determinant of tumor growth and recurrence. We define a non-angiogenic, autocrine function for the vascular endothelial growth factor-A (VEGF-A) in regulating Snail expression in breast tumor cells. The transfection of well-differentiated breast tumor cells with VEGF-A increases Snail mRNA and protein levels, resulting in reduced E-cadherin expression. Conversely, reducing endogenous VEGF-A expression in poorly differentiated breast tumor cells by siRNA transfection decreases Snail levels. Our studies demonstrate that VEGF and the VEGF receptor Neuropilin-1 increase Snail expression by suppressing the Glycogen Synthase Kinase-3 (GSK-3), an established inhibitor of Snail transcription and protein stability. The VEGF-A neutralizing antibody Avastin was recently approved by the FDA for the treatment of metastatic breast cancer. We present the provocative finding that beyond its anti-angiogenic activity, Avastin can reduce Snail expression in breast tumor cells. Collectively, this work describes a novel autocrine function for VEGF in breast tumor cells in driving the expression of Snail, a breast tumor progression factor. Based on our demonstration that Avastin reduces Snail expression in breast tumor cells, we propose that the treatment of early stage breast cancer patients with Avastin may impede tumor progression.
• dc.description.sponsorship This work was supported by NIH grant CA093855 (R.E.B.) and a pilot award (R.E.B.) from the Duke Comprehensive Cancer Center's Breast and Ovarian Oncology Research Program
• dc.format.mimetype application/pdf
• dc.identifier.citation Wanami LS, Chen HY, Peiró S, García de Herreros A, Bachelder RE. Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: implications for tumor progression. Exp Cell Res. 2008 Aug 1;314(13):2448-53. DOI: 10.1016/j.yexcr.2008.05.004
• dc.identifier.doi http://dx.doi.org/10.1016/j.yexcr.2008.05.004
• dc.identifier.issn 0014-4827
• dc.identifier.uri http://hdl.handle.net/10230/36422
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Experimental Cell Research. 2008 Aug 1;314(13):2448-53
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.yexcr.2008.05.004
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Mama -- Tumors
• dc.subject.other Expressió gènica
• dc.subject.other Factors de transcripció
• dc.subject.other Endoteli vascular
• dc.title Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: implications for tumor progression
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion