Metabolic regulation of histone acetylation by ACLY supports MDR1 expression in colorectal cancer and highlights a targetable vulnerability
C-glucose suggests that perturbation of citrate flux influences ACLY-associated pathways and acetyl-CoA availability. In this context, vitamin C treatment reduces citrate-derived acetyl-CoA and ACLY phosphorylation and is associated with global histone deacetylation and decreased MDR1 expression in vitro and in KRAS-mutant patient-derived xenografts. Together, these findings highlight ACLY-dependent acetyl-CoA production as a potential metabolic vulnerability linked to epigenetic regulation of drug efflux programs in CRC. Targeting this metabolic-chromatin axis may represent a strategy to modulate MDR1-associated chemoresistance.
Authors
- Aiora Cenigaonandia‐Campillo (ORCID: https://orcid.org/0000-0002-4214-4059)
- Marta Selva‐Gimenez (ORCID: https://orcid.org/0000-0003-4084-7356)
- Laura García‐García (ORCID: https://orcid.org/0000-0002-8585-849X)
- Jesus García-Foncillas
- Lara Sanz-Criado (ORCID: https://orcid.org/0000-0002-9298-2165)
- Anxo Río-Vilariño (ORCID: https://orcid.org/0000-0002-2532-7056)
- Arancha Cebrián (ORCID: https://orcid.org/0000-0002-6260-1376)
- Natalia Baños‐Herraiz
- Lorena Mozas‐Vivar
- Ana Garcia‐Bautista
- María Jesús Fernández-Aceñero
- Óscar Aguilera
- Raquel Perez-Antolín
- Estrella Núñez-Delicado
Institutions
- Hospital Clínico San Carlos (ES)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- Universidad Autónoma de Madrid (ES)
- Universidad Católica de Murcia (ES)
Publication Details
- Journal
- Neoplasia
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1016/j.neo.2026.101314
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00