New role of PTGES3 uncovered in liver cancer growth and immune evasion

by Wang Nianfei and Zhao Weiwei, Chinese Academy of Sciences

edited by Sadie Harley, reviewed by Andrew Zinin

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A research team led by Prof. Wang Hongzhi at the Hefei Institutes of Physical Science, Chinese Academy of Sciences, has found a novel role of prostaglandin E synthase 3 (PTGES3) in liver cancer, revealing how it drives both tumor growth and immune suppression.

The study was published in Molecular Biomedicine.

Hepatocellular carcinoma (HCC) is a highly lethal liver cancer with limited treatment outcomes. Understanding the key regulators of tumor progression and immune suppression is important for improving therapy.

In this study, PTGES3, a cytoplasmic co-chaperone of HSP90, was identified as a nuclear transcriptional regulator. It was significantly overexpressed in HCC and was associated with poor patient outcomes.

PTGES3 promoted the growth and spread of HCC cells through the PI3K/AKT/mTOR pathway. In a diethylnitrosamine (DEN)-induced mouse model, reducing Ptges3 in liver cells significantly suppressed tumor growth. Single-cell RNA sequencing further showed that lower Ptges3 levels reshaped the tumor immune environment, with fewer M2 macrophages.

PTGES3 activated SP1 by binding to its promoter, leading to increased TGF-β production. This promoted tumor growth and enhanced immune suppression. Blocking TGF-β signaling reversed these effects, suggesting that PTGES3 acts independently of its classical chaperon role.

The findings identify the PTGES3/SP1/TGF-β axis as a potential therapeutic target, offering new strategies for combining targeted therapy with immunotherapy in liver cancer.

More information

Nianfei Wang et al, Nuclear prostaglandin E synthase 3 promotes hepatocellular carcinoma growth with immunosuppressive macrophage polarization via the SP1/TGF-β axis, Molecular Biomedicine (2026). DOI: 10.1186/s43556-026-00431-6

Key medical concepts

Carcinoma, HepatocellularTransforming Growth Factor beta

Clinical categories

OncologyGastroenterology Provided by Chinese Academy of Sciences Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

Citation: New role of PTGES3 uncovered in liver cancer growth and immune evasion (2026, June 26) retrieved 27 June 2026 from https://medicalxpress.com/news/2026-06-role-ptges3-uncovered-liver-cancer.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.