GOLM1 upregulates expression of PD-L1 through EGFR/STAT3 pathway in hepatocellular carcinoma.
Jiuliang Yan, Binghai Zhou, Lei Guo, Zheng Chen, Bo Zhang, Shuang Liu, Wentao Zhang, Mincheng Yu, Yongfeng Xu, Yong‐Sheng Xiao, Jian Zhou, Jia Fan, Hui Li, Qing‐Hai Ye
Abstract
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.