| First Author | Ma J | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 3 | Pages | 504-518.e7 |
| PubMed ID | 30827889 | Mgi Jnum | J:277880 |
| Mgi Id | MGI:6285413 | Doi | 10.1016/j.ccell.2019.01.020 |
| Citation | Ma J, et al. (2019) Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair. Cancer Cell 35(3):504-518.e7 |
| abstractText | 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. |
