N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth

Despite the evidences of elevated expression of Mer tyrosine kinase (MerTK) in multiple human cancers, mechanisms underlying the oncogenic roles of MerTK in hepatocellular carcinoma (HCC) remains undefined. We explored the functional effects of MerTK and N-Glycosylated MerTK on HCC cell survival and tumor growth. Here, we show that MerTK ablation increases reactive oxygen species (ROS) production and promotes the switching from glycolytic metabolism to oxidative phosphorylation in HCC cells, thus suppressing HCC cell proliferation and tumor growth. MerTK is N-glycosylated in HCC cells at asparagine 294 and 454 that stabilizes MerTK to promote oncogenic transformation. Moreover, we observed that nuclear located non-glycosylated MerTK is indispensable for survival of HCC cells under stress. Pathologically, tissue microarray (TMA) data indicate that MerTK is a pivotal prognostic factor for HCC. Our data strongly support the roles of MerTK N- glycosylation in HCC tumorigenesis and suggesting N-glycosylation inhibition as a potential HCC therapeutic strategy.

Automated summary

This study explores the functional effects of MerTK and N-glycosylated MerTK on HCC cell survival and tumor growth, revealing the oncogenic mechanisms of MerTK in hepatocellular carcinoma. It shows that MerTK ablation increases ROS production and promotes the switch from glycolytic metabolism to oxidative phosphorylation, suppressing HCC cell proliferation and tumor growth. N-glycosylation of MerTK at specific sites stabilizes MerTK and promotes oncogenic transformation. The study also highlights the prognostic value of MerTK in HCC and suggests N-glycosylation inhibition as a potential therapeutic strategy.