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

Cell Death Dis 2018 05 1;9(5):490. Epub 2018 May 1.

Institute of Medical Sciences, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-0542-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924755PMC
May 2018
40 Reads

Publication Analysis

Top Keywords

cancer stem-like
16
stem-like properties
16
occurrence radioresistance
12
properties ahr
8
cancer
6
ahr
5
stem-like
5
vital role
4
directly activates
4
plays vital
4
α-ketoglutarate treatment
4
role maintenance
4
promotes cancer
4
ahr promotes
4
ikkα directly
4
maintenance cancer
4
activates stemness-related
4
stemness-related genes
4
aryl hydrocarbon
4
demonstrate aryl
4

Similar Publications