Acetate suppresses tumorigenesis through ACSS2-dependent H2A.Z acetylation in esophageal squamous cell carcinoma.

Acetate inhibits esophageal squamous cell carcinoma growth by activating an ACSS2-dependent H2A.Z acetylation pathway, with low acetate and ACSS2 linked to poor prognosis.

• Why it matters: Understanding the epigenome-metabolome interaction in tumor development is vital for developing targeted therapies, especially since acetate and ACSS2 are known oncogenic factors in other cancers but are less understood in ESCC.
• What they did: The study analyzed human ESCC tissues, revealing decreased acetate and ACSS2 levels, and demonstrated that acetate supplementation suppresses tumor growth through ACSS2-mediated H2A.Z acetylation, which activates tumor suppressor genes like ATM.
• The result: This work uncovers a tumor-suppressive acetate-ACSS2-H2A.Z acetylation-ATM axis, suggesting that targeting H2A.Z epigenetic regulation could be a promising therapeutic approach for ESCC.