| Literature DB >> 27300435 |
Sonam Dolma1, Hayden J Selvadurai2, Xiaoyang Lan3, Lilian Lee2, Michelle Kushida2, Veronique Voisin4, Heather Whetstone2, Milly So2, Tzvi Aviv2, Nicole Park3, Xueming Zhu2, ChangJiang Xu4, Renee Head2, Katherine J Rowland2, Mark Bernstein5, Ian D Clarke6, Gary Bader7, Lea Harrington8, John H Brumell9, Mike Tyers8, Peter B Dirks10.
Abstract
Glioblastomas (GBM) grow in a rich neurochemical milieu, but the impact of neurochemicals on GBM growth is largely unexplored. We interrogated 680 neurochemical compounds in patient-derived GBM neural stem cells (GNS) to determine the effects on proliferation and survival. Compounds that modulate dopaminergic, serotonergic, and cholinergic signaling pathways selectively affected GNS growth. In particular, dopamine receptor D4 (DRD4) antagonists selectively inhibited GNS growth and promoted differentiation of normal neural stem cells. DRD4 antagonists inhibited the downstream effectors PDGFRβ, ERK1/2, and mTOR and disrupted the autophagy-lysosomal pathway, leading to accumulation of autophagic vacuoles followed by G0/G1 arrest and apoptosis. These results demonstrate a role for neurochemical pathways in governing GBM stem cell proliferation and suggest therapeutic approaches for GBM.Entities:
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Year: 2016 PMID： 27300435 PMCID： PMC5968455 DOI： 10.1016/j.ccell.2016.05.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743