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

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...

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Detalles Bibliográficos
Autores principales: Ma, Yan, Chen, Xiaohua, Ding, Ting, Zhang, Hanqun, Zhang, Qiuning, Dai, Huanyu, Zhang, Haibo, Tang, Jianming, Wang, Xiaohu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Regular paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10036104/
https://www.ncbi.nlm.nih.gov/pubmed/36724120
http://dx.doi.org/10.1093/jrr/rrac107
Descripción
Sumario: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.

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