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

被引：10

作者：

Ma, Ya ^{[1
,2
]}

Chen, Xiaohua ^{[2
]}

Ding, Ting ^{[3
]}

Zhang, Hanqun ^{[1
,4
]}

Zhang, Qiuning ^{[5
,6
]}

Dai, Huanyu ^{[7
]}

Zhang, Haibo ^{[8
]}

Tang, Jianming ^{[9
]}

Wang, Xiaohu ^{[1
,5
,6
]}

机构：

[1] Lanzhou Univ, Sch Clin Med 1, Lanzhou 730000, Gansu, Peoples R China

[2] Lanzhou Univ, First Hosp Lanzhou Univ, Dept Radiat Oncol, Lanzhou 730000, Gansu, Peoples R China

[3] Yiyang Cent Hosp, Dept Endocrinol, Yiyang 413000, Hunan, Peoples R China

[4] Guizhou Prov Peoples Hosp, Dept Oncol, Guiyang 550002, Guizhou, Peoples R China

[5] Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China

[6] Lanzhou Heavy Ion Hosp, Lanzhou 730000, Gansu, Peoples R China

[7] First Hosp Lanzhou Univ, Lanzhou Univ, Dept Oncol, Lanzhou 730000, Gansu, Peoples R China

[8] Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Hangzhou Med Coll, Oncol Ctr,Dept Radiat Oncol, Hangzhou 310014, Zhejiang, Peoples R China

[9] Lanzhou Univ, First Hosp Lanzhou Univ, Key Lab Biotherapy & Regenerat Med Gansu Prov, Lanzhou 730000, Gansu, Peoples R China

来源：

JOURNAL OF RADIATION RESEARCH | 2023年 / 64卷 / 02期

基金：

美国国家科学基金会; 中国国家自然科学基金;

关键词：

Lysine acetyltransferase 7 (KAT7); PI3K; AKT signaling; radioresistance; breast cancer; HISTONE ACETYLTRANSFERASE HBO1; ESTROGEN-RECEPTOR; CHROMATIN; CELL; TUMOR; PROLIFERATION; ACETYLATION; ACTIVATION; EXPRESSION; SUBUNIT;

D O I：

10.1093/jrr/rrac107

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：448 / 456

页数：9

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