Open AccessEGFR enhances the stemness and progression of oral cancer through inhibiting autophagic degradation of SOX2
Author(s) -
Lv XiaoXi,
Zheng XiaoYu,
Yu JiaoJiao,
Ma HuaRui,
Hua Cheng,
Gao RunTao
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2772
Subject(s) - cancer research , gefitinib , sox2 , epidermal growth factor receptor , cancer stem cell , egfr inhibitors , autophagy , head and neck squamous cell carcinoma , cancer , stem cell , biology , chemistry , microbiology and biotechnology , head and neck cancer , transcription factor , biochemistry , apoptosis , gene , genetics
Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and correlates with poor prognosis. EGFR has been demonstrated to be associated with cancer stem cell traits in HNSCC. However, the underlying molecular mechanism is far from elucidated. Here, SOX2, one of the most important stem cell markers, was identified as a binding partner and substrate of EGFR. EGFR signaling inhibition decreases SOX2 expression by promoting its autophagic degradation. Mechanistically, EGFR activation induces SOX2 phosphorylation at the Y277 site and reduces its ubiquitination, which inhibits its association with p62 and subsequent autophagic degradation. Gefitinib, an EGFR tyrosine kinase inhibitor, shows in vitro and in vivo protective effects against oral cancer cells that can be reversed through autophagy inhibition. Our study suggests that EGFR plays an important role in the development of cancer stem cells by stabilizing SOX2. Targeting EGFR in combination with conventional chemotherapy might be a promising strategy for the treatment of HNSCC through elimination of cancer stem cells.