VEGF/Neuropilin-2 Regulation of Bmi-1 and Consequent Repression of IGF-IR Define a Novel Mechanism of Aggressive Prostate Cancer
Authors
Goel, Hira LalChang, Cheng
Pursell, Bryan M.
Leav, Irwin
Lyle, Stephen
Xi, Hualin Simon
Hsieh, Chung-Cheng
Adisetiyo, Helty
Roy-Burman, Pradip
Coleman, Ilsa M.
Nelson, Peter S.
Vessella, Robert L.
Davis, Roger J.
Plymate, Stephen R.
Mercurio, Arthur M.
Document Type
Journal ArticlePublication Date
2012-10-01
Metadata
Show full item recordAbstract
We show 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 insulin-like growth factor-1 receptor (IGF-IR) expression and signaling, and the mechanism involves Bmi-1-mediated transcriptional repression of the IGF-IR. This mechanism has significant functional and therapeutic implications that were evaluated. IGF-IR expression positively correlates with PTEN and inversely correlates with NRP2 in prostate tumors. NRP2 is a robust biomarker for predicting response to IGF-IR therapy because prostate carcinomas that express NRP2 exhibit low levels of IGF-IR. Conversely, targeting NRP2 is only modestly effective because NRP2 inhibition induces compensatory IGF-IR signaling. Inhibition of both NRP2 and IGF-IR, however, completely blocks tumor growth in vivo.Source
Cancer Discov. 2012 Oct;2(10):906-921. Epub 2012 Jul 9. Link to article on publisher's site
DOI
10.1158/2159-8290.CD-12-0085Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26293PubMed ID
22777769Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1158/2159-8290.CD-12-0085