| First Author | Jun HJ | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 3116 |
| PubMed ID | 30082792 | Mgi Jnum | J:266252 |
| Mgi Id | MGI:6209042 | Doi | 10.1038/s41467-018-05036-4 |
| Citation | Jun HJ, et al. (2018) A PDGFRalpha-driven mouse model of glioblastoma reveals a stathmin1-mediated mechanism of sensitivity to vinblastine. Nat Commun 9(1):3116 |
| abstractText | Glioblastoma multiforme (GBM) is an aggressive primary brain cancer that includes focal amplification of PDGFRalpha and for which there are no effective therapies. Herein, we report the development of a genetically engineered mouse model of GBM based on autocrine, chronic stimulation of overexpressed PDGFRalpha, and the analysis of GBM signaling pathways using proteomics. We discover the tubulin-binding protein Stathmin1 (STMN1) as a PDGFRalpha phospho-regulated target, and that this mis-regulation confers sensitivity to vinblastine (VB) cytotoxicity. Treatment of PDGFRalpha-positive mouse and a patient-derived xenograft (PDX) GBMs with VB in mice prolongs survival and is dependent on STMN1. Our work reveals a previously unconsidered link between PDGFRalpha activity and STMN1, and highlight an STMN1-dependent cytotoxic effect of VB in GBM. |
