Lu Zhaoyi, Zhou Yandan, Jing Qiancheng
Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People's Republic of China.
Changsha Aier Eye Hospital, Aier Eye Hospital Group, Changsha, Hunan,410000, People's Republic of China.
J Cancer. 2022 Apr 24;13(7):2388-2396. doi: 10.7150/jca.71526. eCollection 2022.
Wnt signaling pathways and autophagy play an essential role in tumor progression. Canonical Wnt signaling pathways in radiation resistance have been studied in the past, but it remains unclear whether the noncanonical Wnt signaling pathways can affect tumor radiation resistance through protective autophagy. Nasopharyngeal carcinoma, a particular subtype of head and neck squamous cell carcinoma, relies on radiation therapy. In this study, we found that radioactive rays could significantly promote the expression of Wnt noncanonical signaling pathways ligands in nasopharyngeal carcinoma, among which Wnt5A was the most markedly altered. We have demonstrated that Wnt5a can reduce the radiation sensitivity of nasopharyngeal carcinoma and experiments. Meanwhile, we found much more greater autophagosomes in overexpressed-Wnt5A nasopharyngeal carcinoma cells by electron microscopy. Further mechanism exploration revealed that Beclin1 is the main target of Wnt5A, and knocking down Beclin1 can partially reduce Wnt5a-induced radiation resistance. By studying Wnt5A-mediated protective autophagy in promoting radiation resistance in nasopharyngeal carcinoma cells, we hope that the Wnt5A and Beclin1 can become effective targets for overcoming radiation resistance in the future.
Wnt信号通路和自噬在肿瘤进展中起着至关重要的作用。过去已经对辐射抗性中的经典Wnt信号通路进行了研究，但尚不清楚非经典Wnt信号通路是否可以通过保护性自噬影响肿瘤辐射抗性。鼻咽癌是头颈部鳞状细胞癌的一种特殊亚型，依赖放射治疗。在本研究中，我们发现放射射线可显著促进鼻咽癌中Wnt非经典信号通路配体的表达，其中Wnt5A变化最为明显。我们已经证明Wnt5a可降低鼻咽癌的辐射敏感性并进行了实验。同时，通过电子显微镜我们发现在过表达Wnt5A的鼻咽癌细胞中有更多的自噬体。进一步的机制探索表明，Beclin1是Wnt5A的主要靶点，敲低Beclin1可部分降低Wnt5a诱导的辐射抗性。通过研究Wnt5A介导的保护性自噬在促进鼻咽癌细胞辐射抗性中的作用，我们希望Wnt5A和Beclin1将来能够成为克服辐射抗性的有效靶点。
