Yan Jiuliang, Zhou Binghai, Guo Lei, Chen Zheng, Zhang Bo, Liu Shuang, Zhang Wentao, Yu Mincheng, Xu Yongfeng, Xiao Yongsheng, Zhou Jian, Fan Jia, Li Hui, Ye Qinghai
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education Shanghai 200032, People's Republic of China.
Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University Nanchang 330006, People's Republic of China.
Am J Cancer Res. 2020 Nov 1;10(11):3705-3720. eCollection 2020.
GOLM1, a type II transmembrane protein, is associated with tumor progression, metastasis and immunosuppression. However, the relationship between GOLM1 and the immunosuppressive molecule PD-L1 in HCC remains largely unclear. Here, we revealed that GOLM1 acts as a novel positive regulator of PD-L1, whose abnormal expression plays a crucial role in cancer immune evasion and progression. We found that GOLM1 is overexpressed and positively correlated with PD-L1 expression in HCC. Mechanistically, we found that GOLM1 promotes the phosphorylation of STAT3 by enhancing the level of EGFR, which in turn upregulates the transcriptional expression of PD-L1. Taken together, we demonstrated that GOLM1 acts as a positive regulator of PD-L1 expression via the EGFR/STAT3 signaling pathway in human HCC cells. This study provides a new insight into the regulatory mechanism of PD-L1 expression in HCC, which may provide a novel therapeutic target for HCC immunotherapy.
GOLM1是一种II型跨膜蛋白,与肿瘤进展、转移和免疫抑制相关。然而,GOLM1与肝癌中免疫抑制分子PD-L1之间的关系在很大程度上仍不清楚。在此,我们揭示GOLM1作为PD-L1的一种新型正调节因子,其异常表达在癌症免疫逃逸和进展中起关键作用。我们发现GOLM1在肝癌中过表达且与PD-L1表达呈正相关。机制上,我们发现GOLM1通过提高EGFR水平促进STAT3磷酸化,进而上调PD-L1的转录表达。综上所述,我们证明GOLM1在人肝癌细胞中通过EGFR/STAT3信号通路作为PD-L1表达的正调节因子。本研究为肝癌中PD-L1表达的调控机制提供了新的见解,这可能为肝癌免疫治疗提供新的治疗靶点。