Activation of AhR with nuclear IKKα regulates cancer stem-like properties in the occurrence of radioresistance

被引：41

作者：

Yan, Bin ^{[1
,2
,3
]}

Liu, Shuang ^{[1
,2
]}

Shi, Ying ^{[2
,3
]}

Liu, Na ^{[2
,3
]}

Chen, Ling ^{[2
,3
]}

Wang, Xiang ^{[4
]}

Xiao, Desheng ^{[5
]}

Liu, Xiaoli ^{[2
,3
]}

Mao, Chao ^{[2
,3
]}

Jiang, Yiqun ^{[2
,3
]}

Lai, Weiwei ^{[2
,3
]}

Xin, Xing ^{[2
,3
]}

Tang, Can-E ^{[3
]}

Luo, Dixian ^{[6
]}

Tan, Tan ^{[6
]}

Jia, Jiantao ^{[7
]}

Liu, Yating ^{[2
,3
]}

Yang, Rui ^{[2
,3
]}

Huang, Jun ^{[8
]}

Zhou, Hu ^{[9
]}

Cheng, Yan ^{[10
]}

Cao, Ya ^{[2
,3
]}

Yu, Weishi ^{[11
]}

Muegge, Kathrin ^{[1
,2
,3
,4
]}

Tao, Yongguang ^{[1
,2
,3
,4
]}

机构：

[1] Cent S Univ, Xiangya Hosp, Inst Med Sci, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China

[2] Cent S Univ, Xiangya Hosp, Minist Educ, Key Lab Carcinogenesis & Canc Invas, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China

[3] Cent S Univ, Canc Res Inst, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China

[4] Cent S Univ, Xiangya Hosp 2, Dept Thorac Surg, Changsha, Hunan, Peoples R China

[5] Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha 410008, Hunan, Peoples R China

[6] Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, Natl & Local Joint Engn Lab High Throughput Mol D, 102 Luojiajing Rd, Chenzhou 423000, Hunan, Peoples R China

[7] Changzhi Med Coll, Dept Pathophysiol, Changzhi, Shanxi, Peoples R China

[8] Cent S Univ, Xiangya Hosp, Dept Neurosurg, 87 Xiangya Rd, Changsha 410078, Hunan, Peoples R China

[9] Chinese Acad Sci, Shanghai Inst Mat Med, 555 Chongzhi Rd,Zhangjiang Hi Tech Pk, Shanghai 201203, Peoples R China

[10] Cent S Univ, Sch Pharmaceut Sci, Dept Pharmacol, Changsha 410078, Hunan, Peoples R China

[11] Cipher Gene Beijing Co Ltd, Beijing 100089, Peoples R China

来源：

CELL DEATH & DISEASE | 2018年 / 9卷

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

ARYL-HYDROCARBON RECEPTOR; NF-KAPPA-B; TO-MESENCHYMAL TRANSITION; CELLS; METASTASIS; LIGANDS; EXPRESSION; SURVIVAL; KINASE; MARKER;

D O I：

10.1038/s41419-018-0542-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Most cancer patients receive radiotherapy in the course of their disease and the occurrence of radioresistance is associated with poor prognosis. The molecular pathways that drive enhanced tumorigenic potential during the development of radioresistance are poorly understood. Here, we demonstrate that aryl hydrocarbon receptor (AhR) plays a vital role in the maintenance of cancer stem-like properties. AhR promotes the cancer stem-like phenotype and drives metastasis by directly targeting the promoters of 'stemness' genes, such as the ATP-binding cassette sub-family G member 2 (ABCG2) gene. Moreover, the radioresistant sublines display high levels of oncometabolites including alpha-ketoglutarate, and treatment of cancer cells with alpha-ketoglutarate enhances their stem-like properties in an AhR activation-dependent manner. IKK alpha directly activates stemness-related genes through an interaction with AhR as a bone fide chromatin modifier. Thus, AhR is functionally linked with cancer stem-like properties, and it drives tumorigenesis in the occurrence of radioresistance.

引用

页数：15

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