What does this research mean for the field?

The ENO1-H4K12la-PCNA metabolic-epigenetic axis drives the activation of quiescent breast cancer stem-like cells in triple-negative breast cancer, promoting tumor growth and correlating with poor patient survival. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

Investigate the metabolic and epigenetic mechanisms driving the activation of quiescent breast cancer stem-like cells in triple-negative breast cancer.

August 23, 2026Signal Transduction and Targeted TherapyOpen Access

Glycolytic enolase 1-induced H4K12 lactylation activates quiescent breast cancer stem-like cells in triple-negative breast cancer

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Authors

SLShuai LiuSun Yat-sen University YMYunfeng MaThird Affiliated Hospital of Zhengzhou University YZYujie ZengDalian Medical University

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Implication

Preclinical study reveals ENO1-driven H4K12 lactylation activates quiescent cancer stem-like cells via PCNA in triple-negative breast cancer, indicating a metabolic target.

Key Points

Investigate the metabolic and epigenetic mechanisms driving the activation of quiescent breast cancer stem-like cells in triple-negative breast cancer.
Developed a dual-reporter NANOG-EGFP and H2B-mCherry pulse-chase system to separate quiescent from active breast cancer stem-like cells in vitro and in vivo.
Performed single-cell RNA sequencing on triple-negative breast cancer patient samples and conducted genetic/pharmacological perturbations in orthotopic mouse models.
Identified a positive feedback loop where glycolytic enolase 1 increases lactate and H4K12 lactylation, which in turn enhances PCNA transcription to activate quiescent breast cancer stem-like cells.
Genetic depletion of ENO1 or pharmacological inhibition of lactate production suppressed quiescent stem-like cell activation and attenuated tumor growth in orthotopic mice.
High clinical expression of ENO1 strongly correlated with PCNA and predicted poorer overall survival, recurrence-free survival, and distant metastasis-free survival.

Cite This Study

Liu et al. (2026) studied this question.

synapsesocial.com/papers/6a8aadd57677a341144463ff https://doi.org/10.1038/s41392-026-02916-w

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Implication

Preclinical study reveals ENO1-driven H4K12 lactylation activates quiescent cancer stem-like cells via PCNA in triple-negative breast cancer, indicating a metabolic target.

Glycolytic enolase 1-induced H4K12 lactylation activates quiescent breast cancer stem-like cells in triple-negative breast cancer

Discussion

Member takes

Implication

Key Points

Cite This Study

Glycolytic enolase 1-induced H4K12 lactylation activates quiescent breast cancer stem-like cells in triple-negative breast cancer

Discussion

Member takes

Implication

Key Points

Cite This Study

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