Neuropilin-1-dependent regulation of EGF-receptor Signaling

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

70 Citazioni (Scopus)

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. ©2012 AACR.
Lingua originaleEnglish
pagine (da-a)5801-5811
Numero di pagine11
RivistaCancer Research
Volume72
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • CANCER CELLS
  • EGFR
  • Neuropilin-1 (Nrp1)

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