Aberrant Proliferation in CXCR7+ Endothelial Cells via Degradation of the Retinoblastoma Protein

Jennifer E. Totonchy, Jessica M. Osborn, Sara Botto, Lisa Clepper, Ashlee V. Moses

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor suppressor protein Rb. These findings identify a heretofore unappreciated role for CXCR7 in vascular dysfunction and confirm this receptor as a plausible target for anti-tumor therapy.

Original languageEnglish (US)
Article numbere69828
JournalPloS one
Volume8
Issue number7
DOIs
StatePublished - Jul 23 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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