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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wanami, LS; Chen, H-Y; Peiró, S; García de Herreros, A; Bachelder, RE

Published Date

  • August 1, 2008

Published In

Volume / Issue

  • 314 / 13

Start / End Page

  • 2448 - 2453

PubMed ID

  • 18554584

Pubmed Central ID

  • 18554584

Electronic International Standard Serial Number (EISSN)

  • 1090-2422

Digital Object Identifier (DOI)

  • 10.1016/j.yexcr.2008.05.004

Language

  • eng

Conference Location

  • United States