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Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair.

Cancer Cell. 2019;

Ma J, Benitez JA, Li J, Miki S, Ponte de Albuquerque C, Galatro T, Orellana L, Zanca C, Reed R, Boyer A, Koga T, Varki NM, Fenton TR, Nagahashi Marie SK, Lindahl E, Gahman TC, Shiau AK, Zhou H, DeGroot J, Sulman EP, Cavenee WK, Kolodner RD, Chen CC, Furnari FB.

Products/Services Used	Details	Operation
Peptide Synthesis	Fenton N/A Peptide for pY240-PTEN mouse monoclonal antibody: CTRREDKFMpYFEFPQ This paper Custom synthesis by GenScript Ki-67 WT peptide around KiR-SLIM: ELFDENLPPNTPLKRGEAPTK This paper Custom synthesis by ThermoFisherScientiﬁc Ki-67 mutant peptide around KiR-SLIM: ELFRKNLPPNTPLDEGKAPTE This paper Custom synthesis by ThermoFisherScientiﬁc Pulsin kit for peptide transfection Polyplus-transfection Cat # 501-04 Critical Commercial Assays CometAssay Reagent kit Trevigen Cat # 4250-050-K Subcellular Protein Fractionation Kit for Cultured Cells ThermoFisher Scientiﬁc Cat# 78840 Deposited Data Mass spectrum raw data This paper MassIVE: MSV000081423 http://massive.	Get A Quote

摘要

Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated p... More