NUAK1 acts as a novel regulator of PD-L1 via activating GSK-3β/β-catenin pathway in hepatocellular carcinoma

• DOI: 10.1186/s10020-025-01088-7
• Publication Date: 2025-02-03T09:19:53Z
• Authors: Chao-Yan Yao; Hang-Tian Tao; Jin-Jin He; Feng-Yi Zhu; Cui-Qing Xie; Yu-Na Cheng; Ji-Qin Li; Zhuang-Zhuang Liu; Chun-Yu Hou; Xue-Li Liu; Yong-Li Fan; Dong Fang; Xin-Rui Lv
• Keywords: PD-L1; Hepatocellular carcinoma; Research; NUAK1; GSK3β; Therapeutics. Pharmacology; RM1-950; QD415-436; Β-catenin; Biochemistry

Abstract Background NUAK1 is associated with metastasis and drug resistance in hepatocellular carcinoma (HCC). However, little known about the immune functions of HCC. Therefore, aim this study was to elucidate novel role facilitating evasion HCC investigate mechanisms underpinning process. Method The levels expression infiltration CD8 + T cells were assessed tumor tissues from patients mice xenograft model. cell lines used validate regulating transcription PD-L1, diethylnitrosamine-induced model established PD-L1 proteins rat livers detected. Western blotting, immunofluorescence, real time PCR, immunohistochemical staining underlying by which regulates carcinoma. Results negatively correlated Both gain loss have identified promoted at transcriptional level cells. increased observed Moreover, overexpression promotes GSK3β Ser 9 phosphorylation, β-catenin nuclear accumulation By contrast, knockdown has opposite effects. Inhibition activity significantly IHC analyses suggested that p-GSK3β positively expression. Knockdown also reversed NUAK1-mediated Conclusions This revealed a for NUAK1, activating GSK3β/β-catenin signaling pathway, leading escape Registry registration no. study/trial : Not applicable.