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 pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.
Pubmed ID: 30827889 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsThis monoclonal targets Vimentin
View all literature mentionsThis polyclonal targets ATR, phospho (Ser428)
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis monoclonal targets Phosphotyrosine
View all literature mentionsThis monoclonal targets MEK1/2 (D1A5) Rabbit mAb
View all literature mentionsThis monoclonal targets Sodium Potassium ATPase
View all literature mentionsThis monoclonal targets Actin, beta
View all literature mentionsThis monoclonal targets SUMO-2/3
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis monoclonal targets Phospho-S6 Ribosomal Protein (Ser235/236) (D57.2.2E) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473) (193H12) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-EGF Receptor (Tyr1068)
View all literature mentionsThis monoclonal targets EGF Receptor
View all literature mentionsThis monoclonal targets Chk2 (D9C6) XP Rabbit mAb
View all literature mentionsThis monoclonal targets beta-Tubulin
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets ATM protein
View all literature mentionsThis monoclonal targets ATM (D2E2) Rabbit mAb
View all literature mentionsThis monoclonal targets Histone H3
View all literature mentionsThis polyclonal targets H3f3a
View all literature mentionsThis polyclonal targets Lamin A/C
View all literature mentionsThis polyclonal targets Human MKI67
View all literature mentionsThis polyclonal targets RPA2
View all literature mentionsMus musculus with name FVB/N-Tg(EIIa-cre)C5379Lmgd/J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsMus musculus with name FVB.129-Cdkn2atm1Rdp/Nci from IMSR.
View all literature mentionsMus musculus with name Crl:NU-Foxn1nu from IMSR.
View all literature mentionsCell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets ATR, phospho (Ser428)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name FVB/N-Tg(EIIa-cre)C5379Lmgd/J from IMSR.
View all literature mentionsThis monoclonal targets Vimentin
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsMus musculus with name Crl:NU-Foxn1nu from IMSR.
View all literature mentionsMus musculus with name FVB.129-Cdkn2atm1Rdp/Nci from IMSR.
View all literature mentionsThis polyclonal targets Human MKI67
View all literature mentions