PAG1 promotes the inherent radioresistance of laryngeal cancer cells via activation of STAT3
作者单位：Department of Clinical Oncology Taihe Hospital Hubei University of Medicine Department of Biochemistry School of Basic Medical Sciences Hubei University of Medicine
会议名称：《2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛》
会议日期：2018年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：PAG1 inherent radioresistance STAT3 laryngeal cancer
摘 要：Phosphoprotein associated with glycosphingolipid-enriched microdomains 1(PAG1) is a ubiquitous protein that is essential for the development and progression of various malignancies. A previous study in our laboratory confirmed that PAG1 plays an important role in modulating the inherent radioresistance of laryngeal cancer cells, but the underlying mechanisms are still poorly defined. In this study, we found that PAG1 was significantly increased in laryngeal cancer tissues compared to adjacent non-tumor tissues(P 0.05). The expression of PAG1 was positively correlated with lymph node metastasis(P 0.05) and TNM stage(P 0.05). High expression of PAG1 also predicted a poor prognosis in patients with laryngeal cancer. Moreover, gain-of-function and loss-of-function studies showed that PAG1 overexpression was able to promote growth, increase migration and invasion, and enhance inherent radioresistance of laryngeal cancer cells. Mechanistic investigations revealed that the activation of STAT3 was required for PAG1-mediated inherent radioresistance of laryngeal cancer. Inhibition of STAT3 activity with a chemical inhibitor sensitized radioresistant cells to radiation. Importantly, PAG1-integrin β1 complex was involved in the regulation of STAT3 activation. In addition, downregulation of PAG1 could suppress tumor growth and reverse inherent radioresistance in the nude mouse xenograft model. Taken together, these results suggested that PAG1 conferred inherent radioresistance by activating STAT3, which provided a novel therapeutic strategy for laryngeal cancer.