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Paxillin controls endothelial cell migration and tumor angiogenesis by altering neuropilin 2 expression. J Cell Sci 2014 Apr 15;127(Pt 8):1672-83

Date

02/14/2014

Pubmed ID

24522185

Pubmed Central ID

PMC3986673

DOI

10.1242/jcs.132316

Scopus ID

2-s2.0-84898913240 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

Although a number of growth factors and receptors are known to control tumor angiogenesis, relatively little is known about the mechanism by which these factors influence the directional endothelial cell migration required for cancer microvessel formation. Recently, it has been shown that the focal adhesion protein paxillin is required for directional migration of fibroblasts in vitro. Here, we show that paxillin knockdown enhances endothelial cell migration in vitro and stimulates angiogenesis during normal development and in response to tumor angiogenic factors in vivo. Paxillin produces these effects by decreasing expression of neuropilin 2 (NRP2). Moreover, soluble factors secreted by tumors that stimulate vascular ingrowth, including vascular endothelial growth factor (VEGF), also decrease endothelial cell expression of paxillin and NRP2, and overexpression of NRP2 reverses these effects. These results suggest that the VEGF-paxillin-NRP2 pathway could represent a new therapeutic target for cancer and other angiogenesis-related diseases.

Author List

German AE, Mammoto T, Jiang E, Ingber DE, Mammoto A

Authors

Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carcinoma, Lewis Lung
Cell Line, Tumor
Cell Movement
Gene Expression
Gene Expression Regulation, Neoplastic
Human Umbilical Vein Endothelial Cells
Humans
Mice, Inbred C57BL
Neoplasm Transplantation
Neovascularization, Pathologic
Neuropilin-2
Paxillin
Retinal Vessels
Vascular Endothelial Growth Factor A