# TRIM8-dependent K63-ubiquitinated PGK1 promotes glycolysis and angiogenesis in gastric cancer via interaction with ACAT1

## TL;DR

This study reveals how TRIM8 and PGK1 regulate glycolysis and angiogenesis in gastric cancer, offering a new target for treatment.

## Contribution

The paper identifies a novel TRIM8-dependent K63 ubiquitination mechanism linking glycolysis to tumor angiogenesis in gastric cancer.

## Key findings

- TRIM8 promotes K63-linked ubiquitination of PGK1, enhancing its stability and glycolytic activity.
- PGK1 acetylation via ACAT1 interaction increases lactate production and endothelial cell migration.
- TRIM8 levels correlate with tumor angiogenesis and poor prognosis in gastric cancer patients.

## Abstract

Glycolysis is crucial for promoting cancer progression. However, the precise mechanism underlying glycolysis regulating the angiogenic process remains to be defined. Here, we demonstrate that in human gastric cancer cells, the E3 ligase TRIM8 promotes the K63-linked ubiquitination of the glycolytic enzyme PGK1 and improves its stability, which leads to acetyltransferase ACAT1 recruitment, increased interaction of PGK1 with ACAT1, and subsequent PGK1 acetylation-dependent glycolytic activity. This activity facilitates PGK1-mediated glycolysis, lactate accumulation and triggers a significant increase in endothelial cell migration and tube formation, which ultimately accelerates tumor angiogenesis in gastric cancer. TRIM8 levels are positively correlated with tumor angiogenesis and poor prognosis in gastric cancer patients. These findings elucidate a novel mechanism underlying the upregulation of angiogenesis mediated by K63 ubiquitination-regulated glycolysis in tumor cells and provide a molecular basis for eliminating gastric cancer angiogenesis by targeting TRIM8-dependent PGK1 K63 ubiquitination.