Activation of AMPK inhibits cervical cancer growth by hyperacetylation of H3K9 through PCAF

Sep 22, 2026

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Dysregulated histone acetylation drives cancer epigenetics, yet the AMPK-related epigenetic mechanism in cervical cancer remains unclear. This study evaluates metformin, an AMPK activator, using cell viability assays, tumor xenograft models, pan-acetylation analysis, and the AMPK–PCAF–H3K9ac signaling pathway. Label-free quantitative acetyl proteomics and ChIP-seq test whether AMPK-induced H3K9 acetylation rewires chromatin and tumor-suppressor gene transcription in vitro and in vivo.

LanguageEnglish

CategoryHealthcare

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Pages19

Reading Time48 min

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Abstract

Background

Methods

Results

Conclusions

Background

Pan etal. Cell Communication and Signaling (2024) 22:306 [https://doi.org/10.1186/s12964-024-01687-7](https://doi.org/10.1186/s12964-024-01687-7) Cell Communication and Signaling RESEARCH Open Access Activation of AMPK inhibits cervical cancer growth by hyperacetylation of H3K9 through PCAF Botao Pan 1, Can Liu2, Jiyan Su 1 and Chenglai Xia 1,2* Abstract Background Dysregulation in histone acetylation, a significant epigenetic alteration closely associated with major pathologies including cancer, promotes tumorigenesis, inactivating tumor-suppressor genes and activating oncogenic pathways. AMP-activated protein kinase (AMPK) is a cellular energy sensor that regulates a multitude of biological processes. Although a number of studies have identified the mechanisms by which AMPK regulates cancer growth, the underlying epigenetic mechanisms remain unknown. Methods The impact of metformin, an AMPK activator, on cervical cancer was evaluated through assessments of cell viability, tumor xenograft model, pan-acetylation analysis, and the role of the AMPK-PCAF-H3K9ac signaling pathway. Using label-free quantitative acetyl proteomics and chromatin immunoprecipitation-sequencing (ChIP) technology, the activation of AMPK-induced H3K9 acetylation was further investigated. Results In this study, we found that metformin, acting as an AMPK agonist, activates AMPK, thereby inhibiting the proliferation of cervical cancer both in vitro and in vivo. Mechanistically, AMPK activation induces H3K9 acetylation at epigenetic level, leading to chromatin remodeling in cervical cancer. This also enhances the binding of H3K9acto the promoter regions of multiple tumor suppressor genes, thereby promoting their transcriptional activation. Furthermore, the absence of PCAF renders AMPK activation incapable of inducing H3K9 acetylation. Conclusions In conclusion, our findings demonstrate that AMPK mediates the inhibition of cervical cancer growth through PCAF-dependent H3K9 acetylation. This discovery not only facilitates the clinical application of metformin but also underscores the essential role of PCAF in AMPK activation-induced H3K9 hyperacetylation. Keywords AMP-activated protein kinase (AMPK), H3K9ac, Cervical cancer, PCAF, Histone acetylation *Correspondence: Chenglai Xia [xiachenglai@smu.edu.cn](xiachenglai@smu.edu.cn) 1Foshan Women and Children Hospital, Foshan 528000, China 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 515150, China © The Author(s) 2024, corrected publication 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons](http://creativecommons). org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Pan et al. Cell Communication and Signaling (2024) 22:306 Background Cervical cancer is considered one of the most prevalent cancers among women, with approximately 300,000 fatalities and 600,000 new cases recorded annually on a global scale [1]. The identification of the causative pathoge

FAQs

What is the study’s main finding about metformin and cervical cancer growth?

Metformin, acting as an AMPK agonist, activates AMPK and inhibits cervical cancer proliferation in vitro and in vivo.

How does AMPK activation affect histone acetylation in this work?

AMPK activation induces H3K9 acetylation, causing chromatin remodeling in cervical cancer and enhancing transcription of tumor suppressor genes.

What role does PCAF play in AMPK activation-induced H3K9 hyperacetylation?

When PCAF is absent, AMPK activation cannot induce H3K9 acetylation, indicating a PCAF-dependent mechanism.

Sep 22, 2026

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