Antagonizing CDK8 Sensitizes Colorectal Cancer to Radiation Through Potentiating the Transcription of e2f1 Target Gene apaf1

doi:10.3389/fcell.2020.00408

	Antagonizing CDK8 Sensitizes Colorectal Cancer to Radiation Through Potentiating the Transcription of e2f1 Target Gene apaf1
	Chen, Bin 1,2; Wen, Pengbo 1,2; Hu, Guanshuo 1,2; Gao, Yang 1,2; Qi, Xiaojing 1,2; Zhu, Kaili 1,2; Chen, Shaopeng 1; Wu, Lijun 1; Xu, An 1; Zhao, Guoping 1
刊名	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
	2020-06-12
卷号	8
关键词	CDK8 transcriptional regulation e2f1 apaf1 radiotherapy apoptosis
ISSN号	2296-634X
DOI	10.3389/fcell.2020.00408
通讯作者	Zhao, Guoping(gpz@ipp.ac.cn)
英文摘要	Radiotherapy is an essential curative treatment modality for colorectal cancer. Apoptosis is the major mechanism of IR-induced cell death and aberrant apoptotic signaling results in radioresistance, which is a hallmark of most, perhaps all, types of human cancers. Potentiating the induction of apoptosis is an emerging strategy for cancer radiotherapy. Here, we determined that targeting CDK8 selectively radiosensitized colorectal cancer through the mitochondria-dependent intrinsic apoptotic signaling, which was mediated through the induction of the transcription of apaf1 that was e2f1- and not p53-dependent. Importantly, the enhanced transcriptional activity of e2f1 was dependent on the kinase activity of CDK8 itself and not on the assembling of the mediator complex. In addition, clinical inhibitor, andin vivostudies confirmed the radiosensitizing effect of CDK8. Our results provide a new targeting strategy to improve the radiotherapy of CRC.
资助项目	National Natural Science Foundation of China[31870845] ; National Natural Science Foundation of China[11835014] ; National Natural Science Foundation of China[31601124] ; CAS Pioneer Hundred Talents Program
WOS关键词	BETA-CATENIN ; KINASE ; POLYMERASE ; APOPTOSIS ; GAMMA-H2AX ; P53 ; SUBCOMPLEX ; ELONGATION ; ACTIVATION ; CLEAVAGE
WOS研究方向	Cell Biology ; Developmental Biology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000543829500001
资助机构	National Natural Science Foundation of China ; CAS Pioneer Hundred Talents Program
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/43151]
专题	中国科学院合肥物质科学研究院
通讯作者	Zhao, Guoping
作者单位	1.Chinese Acad Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, Hefei Inst Phys Sci, Hefei, Peoples R China 2.Univ Sci & Technol China, Hefei, Peoples R China
推荐引用方式 GB/T 7714	Chen, Bin,Wen, Pengbo,Hu, Guanshuo,et al. Antagonizing CDK8 Sensitizes Colorectal Cancer to Radiation Through Potentiating the Transcription of e2f1 Target Gene apaf1[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2020,8.
APA	Chen, Bin.,Wen, Pengbo.,Hu, Guanshuo.,Gao, Yang.,Qi, Xiaojing.,...&Zhao, Guoping.(2020).Antagonizing CDK8 Sensitizes Colorectal Cancer to Radiation Through Potentiating the Transcription of e2f1 Target Gene apaf1.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,8.
MLA	Chen, Bin,et al."Antagonizing CDK8 Sensitizes Colorectal Cancer to Radiation Through Potentiating the Transcription of e2f1 Target Gene apaf1".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 8(2020).