文献类型：期刊文献

英文题名：The DNA-PKcs-primary cilia axis maintains ionizing radiation-induced senescence in tumor cells

作者：Liu, Xiuzhu[1,2];Wei, Li[3,4];Zhang, Rong[1,2];Chen, Jiaxin[1,2];Zhang, Tongshan[5];Hua, Junrui[5];Wang, Jufang[5,6];He, Jinpeng[5,6];Xie, Xiaodong[7]

第一作者：Liu, Xiuzhu

通信作者：Wang, JF[1];He, JP[1];Wang, JF[2];He, JP[2];Xie, XD[3]

机构：[1]Gansu Univ Chinese Med, Sch Basic Med Sci, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou 730000, Peoples R China;[3]Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Peoples R China;[4]Gansu Prov Hosp, Clin Lab, Lanzhou 730000, Peoples R China;[5]Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou 730000, Peoples R China;[6]Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[7]Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

通信机构：[1]corresponding author), Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou 730000, Peoples R China;[2]corresponding author), Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[3]corresponding author), Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Peoples R China.

年份：2026

卷号：58

期号：5

起止页码：1045

外文期刊名：ACTA BIOCHIMICA ET BIOPHYSICA SINICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001778033700001)】；

基金：This work was supported by the grants from the National Natural Science Foundation of China (Nos. 12375355 and 12175289) , the Science and Technology Research Project of Gansu Province (Nos. 24JRRA952, 25JRRA1204, 23JRRA533, and 145RTSA012) , and the Youth Innovation Promotion Association CAS (No. 2021415) .

语种：英文

外文关键词：primary cilia; DNA-PKcs; senescence; ionizing radiation

摘要：Senescence is a cellular response closely associated with genotoxic stress and plays a critical role in determining cell fate following irradiation exposure. Primary cilia, which are sensory organelles on the cell surface, detect and transmit diverse signaling cues. However, the relationship between primary cilia and senescence in long-term cell fate decisions after ionizing radiation remains poorly understood. Here, we show that the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) colocalizes with centromeres during various stages of mitosis, whereas during interphase, phosphorylated DNA-PKcs (p-DNA-PKcs) is confined to the nucleus in tumor cells. Following irradiation exposure, primary cilia are formed and persistently maintained at high levels in senescent tumor cells. Inhibition of DNA-PKcs enhances primary cilia formation, whereas combined inhibition with siDNA-PKcs and irradiation reduces cilia generation. Moreover, chloral hydrate-induced primary cilia removal results in senescent cell death and decreases p-DNA-PKcs protein expression. Notably, treatment with the apoptosis inducer ABT263 also leads to increased cell death and decreased incidence of primary cilia. Inhibition of either primary cilia or DNA-PKcs further enhances the radiosensitivity of tumor cells. These findings suggest that DNA-PKcs contributes to primary cilia formation after irradiation and plays a critical role in both the induction and maintenance of cellular senescence.