N-glycosylation Stabilizes MerTK and Promotes Hepatocellular Carcinoma Tumor Growth

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2022 Jun 21

PMID 35728303

Authors

Yongzhang Liu

Linhua Lan

Yujie Li

Jing Lu

Lipeng He

Yao Deng

Mingming Fei

Jun-Wan Lu

Fugen Shangguan

Ju-Ping Lu

Jiaxin Wang

Liang Wu

Kate Huang

Bin Lu

Affiliations

Soon will be listed here.

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.

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