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PAG1 promotes the inherent radioresistance of laryngeal cancer cells via activation of STAT3

PAG1 promotes the inherent radioresistance of laryngeal canc...

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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

作者： Li Shen Qing Ke Jingjing Chai Chuanyi Zhang Li Qiu Feng Peng Xinzhou Deng Zhiguo Luo Department of Clinical Oncology Taihe Hospital Hubei University of Medicine Department of Biochemistry School of Basic Medical Sciences Hubei University of Medicine

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 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.

关键词： PAG1 inherent radioresistance STAT3 laryngeal cancer

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Altered O-glycosylation is associated with inherent radioresistance and malignancy of human laryngeal carcinoma

Altered O-glycosylation is associated with inherent radiores...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛

作者： Li Shen Lu Meng Yingying Wang Qiwen Duan Li Qiu Feng Peng Zhiguo Luo Xiaoxia Dong Department of Clinical Oncology Taihe HospitalHubei University of Medicine Department of biochemsitry School of Basic Medical SciencesHubei University of Medicine School of Biomedical Engineering Hubei University of Medicine Department of pharmacology School of Basic Medical SciencesHubei University of Medicine

radioresistance(inherent or acquired) remains a major obstacle affecting theclinical outcome of radiotherapy for laryngeal carcinoma. Results from our laboratoryand other groups suggest that aberrant glycosylation contributes to cancer acquiredradioresistance. However, the role of glycosylation in inherent radioresistance oflaryngeal carcinoma has not been fully uncovered. In this study, we investigated theglycan profiling of the inherent radioresistant(Hep-2 max) and radiosensitive(Hep-2 min) cell lines using lectin microarray analysis. The results revealed that the radioresistant cell line Hep-2 max presented higher core 1 type O-glycans than the sensitive one. Further analysis of the O-glycan regulation by benzyl-α-GalNAc application in Hep-2 max cells showed partial inhibition of the O-glycan biosynthesis and increased radiosensitivity. In addition, core 1 β1, 3-galactosyltransferase(C1 GALT1) overexpression in Hep-2 min cells enhanced cell migration, invasion, and radioresistance. Conversely, knockdown of C1 GALT1 in Hep-2 max cells was able to suppress these malignant ***, mechanistic investigations showed that C1 GALT1 modified the O-glycans on integrin β1 and regulated its activity. The glycosylation-mediated radioresistance was further inhibited by anti-integrin β1 blocking antibody. Importantly, we also observed that core 1-type O-glycans expression was correlated with advanced tumor stage, metastasis,and poor survival of laryngeal carcinoma patients. These findings suggest that alteredO-glycosylation can lead to the inherent radioresistance and progression, and therefore may be important for enhancing the efficacy of radiotherapy in laryngeal carcinoma.

关键词： O-glycosylation inherent radioresistance malignancy laryngeal carcinoma

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