DLAT Activates EMT to Promote HCC Metastasis by Regulating GLUT1-mediated Aerobic Glycolysis

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2025 Feb 20

PMID 39979835

Authors

Qian Yin

Yinye Yao

Jiaojiao Ni

Yiwen Zhang

Jia Wu

Hui Zeng

Wei Wu

Wei Zhuo

Jieer Ying

Jingjing Li

Affiliations

Soon will be listed here.

Abstract

Background: Metabolic reprogramming is a hallmark of hepatocellular carcinoma (HCC) progression, driving aberrant cellular processes in response to pathological stimuli. While dihydrolipoyl transacetylase (DLAT) has been implicated in the development of various cancers, its specific role and underlying mechanisms in HCC remain unclear. This study aimed to investigate the expression, function, and mechanistic impact of DLAT in HCC.

Methods: A comprehensive analysis was conducted using RNA sequencing data, tissue microarrays, in vitro and in vivo functional assays, and mechanistic studies to evaluate DLAT expression, its functional role in tumor progression, and associated molecular pathways in HCC.

Results: Our study revealed a significant upregulation of DLAT expression in HCC, which was linked to a poor prognosis. Furthermore, we discovered that DLAT facilitated tumor metastasis by driving metabolic reprogramming in HCC cells. Mechanistically, DLAT was found to enhance glucose transporter 1 (GLUT1) expression via H3K18 acetylation, thereby promoting aerobic glycolysis and epithelial-to-mesenchymal transition (EMT), which subsequently augmented metastasis of HCC both in vitro and in vivo. Finally, we confirmed a positive correlation between DLAT and GLUT1 expression in HCC tissues.

Conclusions: These findings establish DLAT as a key regulator in HCC progression and suggest its potential as a promising predictive biomarker and therapeutic target for improving HCC diagnosis and treatment.

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