| First Author | Goel HL | Year | 2016 |
| Journal | Cell Rep | Volume | 14 |
| Issue | 9 | Pages | 2193-2208 |
| PubMed ID | 26923603 | Mgi Jnum | J:234358 |
| Mgi Id | MGI:5789839 | Doi | 10.1016/j.celrep.2016.02.016 |
| Citation | Goel HL, et al. (2016) P-Rex1 Promotes Resistance to VEGF/VEGFR-Targeted Therapy in Prostate Cancer. Cell Rep 14(9):2193-208 |
| abstractText | Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTEN(pc-/-) transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases the sensitivity of prostate tumors to bevacizumab. These data reveal that prostate tumors harbor cells with stem cell properties that are resistant to inhibitors of VEGF/VEGFR signaling. Combining the use of available VEGF/VEGFR-targeted therapies with P-Rex1 or Rac1 inhibition should improve the efficacy of these therapies significantly. |
