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Publication

MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma.

Cancer cell | 2017

ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy. Inhibiting ATG4B in combination with radiotherapy in treating mice with intracranial GBM xenograft markedly slows tumor growth and provides a significant survival benefit. Our work describes an MST4-ATG4B signaling axis that influences GBM autophagy and malignancy, and whose therapeutic targeting enhances the anti-tumor effects of radiotherapy.

Pubmed ID: 29232556 RIS Download

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Associated grants

Agency: NIMHD NIH HHS, United States
Id: L32 MD010147
Agency: NINDS NIH HHS, United States
Id: R01 NS083767
Agency: NINDS NIH HHS, United States
Id: R01 NS080619
Agency: NINDS NIH HHS, United States
Id: R01 NS095634
Agency: NLM NIH HHS, United States
Id: K99 LM011673
Agency: NCI NIH HHS, United States
Id: R21 CA175875
Agency: NINDS NIH HHS, United States
Id: R01 NS102669
Agency: NCI NIH HHS, United States
Id: R01 CA159467
Agency: NINDS NIH HHS, United States
Id: P30 NS081774
Agency: NINDS NIH HHS, United States
Id: R01 NS093843
Agency: NIAAA NIH HHS, United States
Id: R01 AA021751
Agency: NCI NIH HHS, United States
Id: T32 CA070085
Agency: NCI NIH HHS, United States
Id: P01 CA163205
Agency: NCI NIH HHS, United States
Id: R01 CA111456
Agency: NCI NIH HHS, United States
Id: R01 CA083817
Agency: NLM NIH HHS, United States
Id: R00 LM011673
Agency: NLM NIH HHS, United States
Id: R01 LM012011

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RRID:SCR_005677

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