Dataset Information

N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth.

ABSTRACT: 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9214875 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth.

Liu Yongzhang Y Lan Linhua L Li Yujie Y Lu Jing J He Lipeng L Deng Yao Y Fei Mingming M Lu Jun-Wan JW Shangguan Fugen F Lu Ju-Ping JP Wang Jiaxin J Wu Liang L Huang Kate K Lu Bin B

Redox biology 20220616

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, thu ...[more]

PMID: 35728303

Similar Datasets

Project description:Background: Previous studies have shown that glycosylation of proteins ofen plays an important role in HCC. However, the potential mechanism of glycosylation in HCC has not been described systematically. Methods: We comprehensively evaluated the glycosylation patterns in HCC samples based on 43 glycosylation regulators, and annotated the modification patterns with the enrichment of immune cells and stromal cells. Considering the heterogeneity of HCC patients, the glycosylation score was constructed using single-sample gene set enrichment analysis (ssGSEA). We also explored the drugs that different HCC patients were sensitive to based on glycosylation mode and score. Results: We identified three glycosylation-regulated gene subtypes. By annotating the subtypes, it was found that the glycosylation regulated gene subtypes was highly matched with three immunophenotypes of HCC (immune-inflamed, immune-excluded, and immune-desert), regardless of the characteristics of immune cell infiltration or prognosis. Based on the characteristic genes of glycosylation-regulated gene subtypes, we constructed a glycosylation-related model, and found that glycosylation-related model was highly consistent with the glycosylation regulated gene subtypes. The glycosylation score that evaluates the glycosylation characteristics of a single HCC sample has high prognostic value, and the prognosis of patients with high glycosylation score is significantly worse. Interestingly, we found that the glycosylation score was closely related to tumor node metastasis (TNM) staging. By applying glycosylation-regulated gene subtypes and glycosylation score to explore the sensitivity of different patients to anticancer drugs, it was found that the sensitivity of Thapsigargin, Shikonin, Embelin and Epothilone. B was closely related to the glycosylation mode. Conclusion: This study reveals that the diversity of glycosylation patterns plays an important role in HCC. Therefore, evaluating the glycosylation patterns of patients with HCC will be helpful in identifying the characteristics of immune cell infiltration and selecting accurate treatment methods.

Dataset Information

N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth.

Publications

N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets