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Review
. 2025 Oct;39(10):e70553.
doi: 10.1002/jbt.70553.

SIRT1-FOXO1 Signaling in Cancer

Altaf A Abdulkhaliq  1 , Johra Khan  2 , Amir Ajoolabady  3 , Domenico Pratico  4 , Suhad Bahijri  5   6   7 , Jaakko Tuomilehto  8 , Anwar Borai  9 , Bonglee Kim  10 , Yuan Zhou  11 , Jun Ren  12
Affiliations
Review

SIRT1-FOXO1 Signaling in Cancer

Altaf A Abdulkhaliq et al. J Biochem Mol Toxicol. 2025 Oct.

Abstract

Sirt1 (sirtuin 1) is a member of the sirtuin family of NAD+-dependent histone deacetylases, which mediates the deacetylation of both histone and nonhistone protein substrates, including enzymes and transcription factors. Through this process, Sirt1 regulates gene transcription and activates various cellular functions. FOXO1 (forkhead box protein O1), a key substrate of sirt1, is a transcription factor that controls the expression of genes involved in a wide range of cellular processes. In the context of cancer, the activation of the sirt1-FOXO1 signaling pathway is influenced by various molecular mechanisms, leading to complex and often contradictory outcomes. Depending on the type of malignancy and experimental cell model, this pathway can either promote or inhibit tumorigenesis, cancer progression, drug resistance, and tumor growth. In this perspective, we aim to explore the mechanisms underlying Sirt1-FOXO1 signaling in cancer pathophysiology, tumorigenesis, and drug resistance. We will provide an in-depth discussion of the current in vitro and in vivo data, hoping to shed light on potential new research directions and to contribute to the development of therapeutic strategies, pending further investigation.

Keywords: FOXO1; Sirtuin 1 (sirt1); cancer; drug resistance; gene transcription; intracellular signaling; pathogenesis; tumorigenesis.

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References

    1. R. H. Houtkooper, E. Pirinen, and J. Auwerx, “Sirtuins as Regulators of Metabolism and Healthspan,” Nature Reviews Molecular Cell Biology 13, no. 4 (2012): 225–238.
    1. M. C. Haigis and D. A. Sinclair, “Mammalian Sirtuins: Biological Insights and Disease Relevance,” Annual Review of Pathology: Mechanisms of Disease 5, no. 1 (2010): 253–295.
    1. F. Fiorentino, E. Fabbrizi, A. Mai, and D. Rotili, “Activation and Inhibition of Sirtuins: From Bench to Bedside,” Medicinal Research Reviews 45 (2024): 484–560.
    1. R. Thapa, E. Moglad, M. Afzal, et al., “The Role of Sirtuin 1 in Ageing and Neurodegenerative Disease: A Molecular Perspective,” Ageing Research Reviews 102 (2024): 102545.
    1. Y. You and W. Liang, “SIRT1 and SIRT6: The Role in Aging‐Related Diseases,” Biochimica et Biophysica Acta (BBA)‐Molecular Basis of Disease 1869 (2023): 166815.

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