We demonstrate that the VEGF receptor, neuropilin-2 (NRP2) is associated with high-grade, PTEN-null prostate cancer and that its expression in tumor cells is induced by PTEN loss as a consequence of c-Jun activation.
VEGF/NRP2 signaling represses IGF-1R expression and signaling and the mechanism involves Bmi-1-mediated transcriptional repression of the IGF-1R. This mechanism has significant functional and therapeutic implications that were evaluated. IGF-1R expression correlates with PTEN and inversely with NRP2 in prostate tumors. NRP2 is a robust biomarker for predicting response to IGF-1R therapy because prostate carcinomas that express NRP2 exhibit low levels of IGF-1R. Conversely, targeting NRP2 is only modestly effective because NRP2 inhibition induces compensatory IGF-1R signaling. Inhibition of both NRP2 and IGF-1R, however, completely blocks tumor growth in vivo.
Written by:
Goel HL, Chang C, Pursell B, Leav I, Lyle S, Xi HS, Hsieh CC, Adisetiyo H, Roy-Burman P, Coleman I, Nelson PS, Vessella RL, Davis RJ, Plymate SR, Mercurio AM. Are you the author?
Cancer Biology, University of Massachusetts Medical School.
Reference: Cancer Discov. 2012 Jul 9. Epub ahead of print.
doi: 10.1158/2159-8290.CD-12-0085
PubMed Abstract
PMID: 22777769
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