VEGF exerts an angiogenesis-independent function in cancer cells to promote their malignant progression

Ying Cao, Guangqi E, Enfeng Wang, Krishnendu Pal, Shamit K. Dutta, Dafna Bar-Sagi, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

VEGF/vascular permeability factor (VEGF/VPF or VEGF-A) is a pivotal driver of cancer angiogenesis that is a central therapeutic target in the treatment of malignancy. However, little work has been devoted to investigating functions of VEGF that are independent of its proangiogenic activity. Here, we report that VEGF produced by tumor cells acts in an autocrine manner to promote cell growth through interaction with the VEGF receptor neuropilin-1 (NRP-1). Reducing VEGF expression by tumor cells induced a differentiated phenotype in vitro and inhibited tumor forming capacity in vivo, independent of effects on angiogenesis. Autocrine activation of tumor cell growth was dependent on signaling through NRP-1, and Ras was determined to be a critical effector signaling molecule downstream of NRP-1. Our findings define a novel function for VEGF in dedifferentiation of tumor cells expanding its role in cancer beyond its known proangiogenic function.

Original languageEnglish (US)
Pages (from-to)3912-3918
Number of pages7
JournalCancer research
Volume72
Issue number16
DOIs
StatePublished - Aug 15 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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