title: Paxillin controls endothelial cell migration and tumor angiogenesis by altering neuropilin 2 expression.
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.
authors: Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA 02139, USA.
authors: Alexandra E
authors: AE
authors: German
authors: Tadanori
authors: T
authors: Mammoto
authors: Elisabeth
authors: E
authors: Jiang
authors: Donald E
authors: DE
authors: Ingber
authors: Akiko
authors: A
authors: Mammoto
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology* / Q000637:transplantation; D006801:Humans; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D039943:Neuropilin-2 / Q000235:genetics* / Q000378:metabolism; D051419:Paxillin / Q000502:physiology*; D012171:Retinal Vessels / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D039943:Neuropilin-2; C496061:PXN protein, human; D051419:Paxillin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C581308:neuropilin-2, human
keywords: Angiogenesis; Cancer; Capillary endothelial cell; Motility; Neuropilin 2; Paxillin; VEGF