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J Cell Mol Med. 2019 May 21. doi: 10.1111/jcmm.14394. [Epub ahead of print]

Wnt3a promotes radioresistance via autophagy in squamous cell carcinoma of the head and neck.

Jing Q1,2,3, Li G1,2, Chen X1,2, Liu C1,2, Lu S1,2, Zheng H1,2, Ma H1,2, Qin Y1,2,4, Zhang D1,2, Zhang S1,2, Ren S1,2, Huang D1,2, Tan P5, Chen J5, Qiu Y1,2, Liu Y1,2.

Author information

1
Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
2
Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, People's Republic of China.
3
Department of Otolaryngology Head and Neck Surgery, Changsha Central Hospital, University Of South China, Changsha, Hunan, People's Republic of China.
4
Health Management Center, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
5
Department of Head and Neck Surgery, Hunan Cancer Hospital, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, People's Republic of China.

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:

Wnt3a; autophagy; prognosis; radioresistance; squamous cell carcinoma of the head and neck

PMID:
31111621
DOI:
10.1111/jcmm.14394
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