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Wnt3a promotes radioresistance via autophagy in squamous cell carcinoma of the head and neck
Authors:Qiancheng Jing  Guo Li  Xiyu Chen  Chao Liu  Shanhong Lu  Hua Zheng  Huiling Ma  Yuexiang Qin  Diekuo Zhang  Shuiting Zhang  Shuling Ren  Donghai Huang  Pingqing Tan  Jie Chen  Yuanzheng Qiu  Yong Liu
Abstract:The canonical Wnt/β‐catenin signalling pathway and autophagy play critical roles in cancer progression. However, the role of Wnt‐mediated autophagy in cancer radioresistance remains unclear. In this study, we found that irradiation activated the Wnt/β‐catenin and autophagic signalling pathways in squamous cell carcinoma of the head and neck (SCCHN). Wnt3a is a classical ligand that activated the Wnt/β‐catenin signalling pathway, induced autophagy and decreased the sensitivity of SCCHN to irradiation both in vitro and in vivo. Further mechanistic analysis revealed that Wnt3a promoted SCCHN radioresistance via protective autophagy. Finally, expression of the Wnt3a protein was elevated in both SCCHN tissues and patients' serum. Patients showing high expression of Wnt3a displayed a worse prognosis. Taken together, our study indicates that both the canonical Wnt and autophagic signalling pathways are valuable targets for sensitizing SCCHN to irradiation.
Keywords:autophagy  prognosis  radioresistance  squamous cell carcinoma of the head and neck  Wnt3a
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