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

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

doi:10.1111/jcmm.14394

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

J Cell Mol Med. 2019 Jul;23(7):4711-4722. doi: 10.1111/jcmm.14394. Epub 2019 May 21.

Authors

Qiancheng Jing^{1

2

3}, Guo Li^{1

2}, Xiyu Chen^{1

2}, Chao Liu^{1

2}, Shanhong Lu^{1

2}, Hua Zheng^{1

2}, Huiling Ma^{1

2}, Yuexiang Qin^{1

2

4}, Diekuo Zhang^{1

2}, Shuiting Zhang^{1

2}, Shuling Ren^{1

2}, Donghai Huang^{1

2}, Pingqing Tan⁵, Jie Chen⁵, Yuanzheng Qiu^{1

2}, Yong Liu^{1

2}

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / radiation effects
Beclin-1 / metabolism
Cell Line, Tumor
Electrons
Female
Humans
Male
Mice, Nude
Middle Aged
Proportional Hazards Models
Radiation Tolerance* / radiation effects
Squamous Cell Carcinoma of Head and Neck / metabolism*
Survival Analysis
Wnt Signaling Pathway / radiation effects
Wnt3A Protein / metabolism*

Substances

Beclin-1
Wnt3A Protein