Hedgehog signaling regulates brain tumor-initiating cell proliferation and portends shorter survival for patients with PTEN-coexpressing glioblastomas.

摘要: The identification of brain tumor stem-like cells (BTSCs) has implicated a role biological self-renewal mechanisms in clinical initiation and propagation. molecular underlying the tumor-forming capacity BTSCs, however, remain unknown. Here, we have generated signatures glioblastoma multiforme (GBM) using gene expression profiles BTSCs identified both Sonic Hedgehog (SHH) signaling-dependent -independent their respective surgical specimens. BTSC proliferation could be abrogated pathway-dependent fashion vitro an intracranial model athymic mice. Both SHH-dependent growth required phosphoinositide 3-kinase-mammalian target rapamycin signaling. In human GBMs, levels SHH PTCH1 were significantly higher PTEN-expressing tumors than PTEN-deficient tumors. addition, show that hyperactive SHH-GLI signaling PTEN-coexpressing GBM is associated with reduced survival time. Thus, distinct dependence may underpin propagation by BTSCs. Modeling these provide rationale for individualized treatment.