Open AccessWnt signaling induces radioresistance through upregulating HMGB1 in esophageal squamous cell carcinoma
Author(s) -
Yuanyuan Zhao,
Jun Yi,
Leilei Tao,
Guichun Huang,
Xiaoyuan Chen,
Haiyan Song,
Longbang Chen
Publication year - 2018
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/s41419-018-0466-4
Subject(s) - radioresistance , wnt signaling pathway , dna damage , cancer research , signal transduction , biology , dna repair , microbiology and biotechnology , chromatin , chemistry , cell culture , dna , biochemistry , genetics
Although many articles have uncovered that Wnt signaling is involved in radioresistance, the mechanism is rarely reported. Here we generated two radioresistant cells rECA109 and rKyse150 from parental esophageal cancer cells ECA109 and Kyse150. We then found that Wnt signaling activity was higher in radioresistant cells and was further activated upon ionizing radiation (IR) exposure. In addition, radioresistant cells acquired epithelial-to-mesenchymal transition (EMT) properties and stem quality. Wnt signaling was then found to be involved in radioresistance by promoting DNA damage repair. In our present study, high-mobility group box 1 protein (HMGB1), a chromatin-associated protein, was firstly found to be transactivated by Wnt signaling and mediate Wnt-induced radioresistance. The role of HMGB1 in the regulation of DNA damage repair with the activation of DNA damage checkpoint response in response to IR was the main cause of HMGB1-induced radioresistance.