KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer.

Yan Ma, Xiaohua Chen, Ting Ding, Hanqun Zhang, Qiuning Zhang, Huanyu Dai, Haibo Zhang, Jianming Tang, Xiaohu Wang

Journal of radiation research 2023 Mar 23

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Chromatin-modifying enzymes are commonly altered in cancers, but the molecular mechanism by which they regulate cancers remains poorly understood. Herein, we demonstrated that Lysine acetyltransferase 7 (KAT7) was upregulated in breast cancer. KAT7 expression negatively correlated with the survival of breast cancer patients, and KAT7 silencing suppressed breast cancer radioresistance in vitro. Mechanistically, KAT7 activated Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) transcription, leading to enhanced PI3K/AKT signaling and radioresistance. Overexpression of AKT or PIK3CA restored radioresistance suppression induced by KAT7 inhibition. Moreover, overexpression of KAT7, but not KAT7 acetyltransferase activity-deficient mutants promoted AKT phosphorylation at the Ser473 site, PIK3CA expression and radioresistance suppression due to KAT7 inhibition. In conclusion, KAT7 has huge prospects for clinical application as a new target for predicting radioresistance in breast cancer patients. © The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.

Citation

Yan Ma, Xiaohua Chen, Ting Ding, Hanqun Zhang, Qiuning Zhang, Huanyu Dai, Haibo Zhang, Jianming Tang, Xiaohu Wang. KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer. Journal of radiation research. 2023 Mar 23;64(2):448-456