FGFR2-mediated phosphorylation of PTEN at tyrosine 240 contributes to the radioresistance of glioma
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Ionizing radiation (IR) is a standard-of-care treatment for glioma patients; however, the clinical efficacy is limited due to therapeutic resistance. A recent study published by Ma et al. (Cancer Cell 35:504–518, 2019) reported that the phosphorylation of phosphatase and tensin homolog (PTEN) at tyrosine 240 (pY240-PTEN) promotes the radioresistance of human glioma cells. After treatment with IR, the fibroblast growth factor receptor 2 (FGFR2)-mediated phosphorylation that generated pY240-PTEN could effectively promote the decondensation of chromatin through an interaction with Ki-67, leading to DNA damage repair and radioresistance. However, such promising findings need to be addressed in detail after considering the following points. (1) The authors should take into consideration whether or not the nuclear-cytoplasmic translocalization of PTEN occurs. (2) The roles of FGFR2-PTEN downregulation should be validated using both genetic and pharmacological inhibition models. (3) Some of the data shown by the authors are confusing and did not support the conclusion that patients with higher PTEN and FGFR2 expression were relatively IR resistant.
KeywordsFGFR2 pY240-PTEN Radioresistance Glioma
This work is supported by National Natural Science Foundation of China (No. 81803035, 81703036, 81572946), and China Postdoctoral Science Foundation (No. 2017 M610510).
Conception and design: ZC Gong, YL Yan, and ZJ Xu. Writing, review, and/or revision of the manuscript: YL Yan, Z Li, and ZJ Xu. Administrative, technical, or material support: Z Li, SS Zeng and X Wang.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
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