Neuropilin-1-dependent regulation of EGF-receptor Signaling

Sabrina Rizzolio, Noa Rabinowicz, Elena Rainero, Letizia Lanzetti, Guido Serini, Jim Norman, Gera Neufeld, Luca Tamagnone

Research output: Contribution to journalArticlepeer-review

Abstract

Neuropilin-1 (NRP1) is a coreceptor for multiple extracellular ligands. NRP1 is widely expressed in cancer cells and in advanced human tumors; however, its functional relevance and signaling mechanisms are unclear. Here, we show that NRP1 expression controls viability and proliferation of different cancer cells, independent of its short intracellular tail. We found that the extracellular domain of NRP1 interacts with the EGF receptor (EGFR) and promotes its signaling cascade elicited upon EGF or TGF-α stimulation. Upon NRP1 silencing, the ability of ligand-bound EGFR to cluster on the cell surface, internalize, and activate the downstream AKT pathway is severely impaired. EGFR is frequently activated in human tumors due to overexpression, mutation, or sustained autocrine/paracrine stimulation. Here we show that NRP1-blocking antibodies and NRP1 silencing can counteract ligand-induced EGFR activation in cancer cells. Thus our findings unveil a novel molecular mechanism by which NRP1 can control EGFR signaling and tumor growth.

Original languageEnglish
Pages (from-to)5801-5811
Number of pages11
JournalCancer Research
Volume72
Issue number22
DOIs
Publication statusPublished - Nov 15 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Neuropilin-1-dependent regulation of EGF-receptor Signaling'. Together they form a unique fingerprint.

Cite this