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A PDGFRα-driven mouse model of Glioblastoma reveals a Stathmin1-mediated mechanism of sensitivity to Vinblastine

ABSTRACT: Glioblastoma multiforme (GBM) is an aggressive primary brain cancer that includes focal amplification of PDGFRα 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 PDGFRα and the analysis of GBM signaling pathways using proteomics. We discovered the tubulin-binding protein Stathmin1 (STMN1) as a PDGFRα phospho-regulated target and that this mis-regulation conferred selective sensitivity to vinblastine (VB) cytotoxicity. Treatment of PDGFRα GBMs with VB in mice drastically prolonged survival and was dependent on STMN1. Our work provides a rationale for evaluating genotype-specific anti-microtubule drugs as cancer treatment in select GBM patient populations.

ORGANISM(S): Mus musculus

PROVIDER: GSE114438 | GEO | 2018/05/15

REPOSITORIES: GEO

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