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

Release time:2020-07-13

Impact Factor:5.959

Affiliation of Author(s):中南大学

Journal:Cell Death Dis

Abstract: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 α-ketoglutarate, and treatment of cancer cells with α-ketoglutarate enhances their stem-like properties in an AhR activation-dependent manner. IKKα 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.

Co-author:Ying Shi, Na Liu, Ling Chen, Xiang Wang, Desheng Xiao, Xiaoli Liu,Chao Mao, Yiqun Jiang, Weiwei Lai, Xing Xin, Can-E Tang, Dixian Luo, Tan Tan, Jiantao Jia,Yating Liu, Rui Yang, Jun Huang, Hu Zhou, Yan Cheng, Ya Cao, Weishi Yu, Kathrin Muegge

First Author:Bin Yan

Indexed by:Journal paper

Correspondence Author:Shuang Liu ,Yongguang Tao

Volume:9(5)

Page Number:490

Translation or Not:no

Date of Publication:2018-05-01

Included Journals:SCI