Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 7, Pages 4711-4722Publisher
WILEY
DOI: 10.1111/jcmm.14394
Keywords
autophagy; prognosis; radioresistance; squamous cell carcinoma of the head and neck; Wnt3a
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Funding
- National Natural Science Foundation of China [81602684, 81773243, 81874133]
- Xiangya Hospital-Sinobioway Clinic and rehabilitation Research Foundation [XYWM2015123]
- Natural Science Foundation of Hunan Province [2017JJ3488, 2018JJ2630]
- Huxiang Young Talent Project [2018RS3024]
- National Key Research and Development Program of China [2016YFC0902003]
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The canonical Wnt/beta-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/beta-catenin and autophagic signalling pathways in squamous cell carcinoma of the head and neck (SCCHN). Wnt3a is a classical ligand that activated the Wnt/beta-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.
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