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Publication

Hypoxic Induction of Vasorin Regulates Notch1 Turnover to Maintain Glioma Stem-like Cells.

Cell stem cell | 2018

Tumor hypoxia is associated with poor patient survival and is a characteristic of glioblastoma. Notch signaling is implicated in maintaining glioma stem-like cells (GSCs) within the hypoxic niche, although the molecular mechanisms linking hypoxia to Notch activation have not been clearly delineated. Here we show that Vasorin is a critical link between hypoxia and Notch signaling in GSCs. Vasorin is preferentially induced in GSCs by a HIF1α/STAT3 co-activator complex and stabilizes Notch1 protein at the cell membrane. This interaction prevents Numb from binding Notch1, rescuing it from Numb-mediated lysosomal degradation. Thus, Vasorin acts as a switch to augment Notch signaling under hypoxic conditions. Vasorin promotes tumor growth and reduces survival in mouse models of glioblastoma, and its expression correlates with increased aggression of human gliomas. These findings provide mechanistic insights into how hypoxia promotes Notch signaling in glioma and identify Vasorin as a potential therapeutic target.

Pubmed ID: 29198941 RIS Download

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Associated grants

Agency: NCRR NIH HHS, United States
Id: S10 RR031537
Agency: NCATS NIH HHS, United States
Id: KL2 TR000440
Agency: NIGMS NIH HHS, United States
Id: U54 GM104940
Agency: NINDS NIH HHS, United States
Id: R01 NS094199
Agency: NINDS NIH HHS, United States
Id: R01 NS099175
Agency: NIH HHS, United States
Id: S10 OD019972
Agency: NINDS NIH HHS, United States
Id: R01 NS092641
Agency: NINDS NIH HHS, United States
Id: R01 NS091080
Agency: NCI NIH HHS, United States
Id: R01 CA184090

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GraphPad (tool)

RRID:SCR_000306

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RRID:SCR_005780

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