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Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma.

Overview

Authors: Jilong Liu1,2, Yanfei Sun1,2, Yuehua Zhu1,2, Guangjing Mu1,2, Jiazheng Wang1, Liangliang Wang3, Feihu Zhao3, Zhimin Zhao1,2, Jian Wang1,4, Ying He5, Zheng Jiang1,2, Xingang Li1,2, Mingzhi Han1,2, Bin Huang1,2
ORCID iDs: Jilong Liu, Liangliang Wang, Zheng Jiang, Xingang Li, Mingzhi Han, Bin Huang
  1. Department of Neurosurgery Qilu Hospital Cheeloo College of Medicine and Institute of Brain and Brain‐Inspired Science Shandong University Jinan China
  2. Jinan Microecological Biomedicine Shandong Laboratory Shandong Key Laboratory of Brain Health and Function Remodeling Jinan China
  3. Department of Neurosurgery The Second Qilu Hospital of Shandong University Cheeloo College of Medicine Shandong University Jinan China
  4. Department of Biomedicine University of Bergen Bergen Norway
  5. Research Center for Basic Medical Sciences Qilu Hospital of Shandong University Jinan China
Institutions: Shandong University (China); Qilu Hospital of Shandong University (China); University of Bergen (Norway)
Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany), article e77551
Dates: received 10 January 2026; accepted 22 August 2026; published online 8 September 2026; in print September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/advs.77551 · PMID 42711856 · PMCID PMC13554370 · OpenAlex W7212085792
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: other condition (population)
Methods: Statistics, Connectivity
Keywords: GBM, GSCs, KAT7, OXPHOS, RAC2
Topic: Cancer, Hypoxia, and Metabolism (Cancer Research, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Key R&D Program of Shandong Province (2025CXPT177); National Natural Science Foundation of China (82504154, 82573856); China Postdoctoral Science Foundation (2024M761832); Natural Science Foundation of Shandong Province (ZR2025QC1768, ZR2022MH137); Special Foundation for Taishan Young Scholars (tsqn202211041); Department of Science & Technology of Shandong Province (SYS202202); Taishan Scholars (tshw201502056); Qilu Young Scholar Program of Shandong University
Citations: not cited yet (Europe PMC); 51 references in the paper

Abstract

Glioblastoma multiforme (GBM), the most lethal type of primary brain tumor, exhibits profound metabolic plasticity driven by glioma stem cells (GSCs), which sustain therapeutic resistance and tumor recurrence. Here, we elucidate a novel epigenetic‐metabolic axis mediated by the histone acetyltransferase KAT7 that orchestrates oxidative phosphorylation (OXPHOS) dominance in GSCs. Through a multi‐omics analysis, we demonstrated that KAT7 is preferentially upregulated in GBM, particularly in the classical subtype and in GSC‐enriched populations, where it activates Rac family samll GTPase 2 (RAC2) expression via H3K14 acetylation of its promoter. Mechanistically, KAT7‐mediated RAC2 upregulation triggers PAK1/2/3 phosphorylation, increasing tricarboxylic acid cycle (TCA) and ATP production. Genetic ablation of KAT7 impairs GSCs self‐renewal, induces apoptosis, and suppresses tumor growth in orthotopic xenograft models. Conversely, KAT7 overexpression or pharmacological activation of the KAT7–RAC2 axis restores metabolic fitness and malignant phenotypes. Notably, the small‐molecule inhibitor WM‐3835, which targets KAT7, exhibits potent anti‐GBM efficacy by disrupting H3K14ac and mitochondrial respiration, leading to prolonged survival in mice. Our study identifies KAT7 as a master regulator of GSCs metabolism, revealing an actionable therapeutic target in GBM progression. Targeting the KAT7–RAC2–PAK axis may represent a precise strategy to overcome metabolic plasticity‐driven therapeutic resistance in this recalcitrant malignancy.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Data links

Data Availability Statement

The data that support the findings of this study are openly available in Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/, reference numbers GSE328130, GSE328308.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, pages, dates, 14 authors, 5 keywords, 8 funders, 51 references.

Cite

This paper

Liu, J., Sun, Y., Zhu, Y., Mu, G., Wang, J., Wang, L., Zhao, F., Zhao, Z., Wang, J., He, Y., Jiang, Z., Li, X., Han, M., & Huang, B. (2026). Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e77551. https://doi.org/10.1002/advs.77551

BibTeX

@article{liu2026targeting,
author = {Liu, Jilong and Sun, Yanfei and Zhu, Yuehua and Mu, Guangjing and Wang, Jiazheng and Wang, Liangliang and Zhao, Feihu and Zhao, Zhimin and Wang, Jian and He, Ying and Jiang, Zheng and Li, Xingang and Han, Mingzhi and Huang, Bin},
title = {{Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = sep,
pages = {e77551},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/advs.77551},
url = {https://doi.org/10.1002/advs.77551},
pmid = {42711856},
pmcid = {PMC13554370}
}

RIS

TY - JOUR
AU - Liu, Jilong
AU - Sun, Yanfei
AU - Zhu, Yuehua
AU - Mu, Guangjing
AU - Wang, Jiazheng
AU - Wang, Liangliang
AU - Zhao, Feihu
AU - Zhao, Zhimin
AU - Wang, Jian
AU - He, Ying
AU - Jiang, Zheng
AU - Li, Xingang
AU - Han, Mingzhi
AU - Huang, Bin
TI - Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/09/08
SP - e77551
SN - 2198-3844
PB - Wiley
DO - 10.1002/advs.77551
UR - https://doi.org/10.1002/advs.77551
LA - en
ER -

CSL-JSON

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