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Multidimensional Regulatory Network and Spatiotemporal Specificity of FOXO Transcription Factors in Digestive System

Shuo Cheng1, Shidi Zhang1, Jishu Quan1

  • 1Department of Biochemistry and Molecular Biology, Medical College, Yanbian University, Yanji 133002, China.

International Journal of Molecular Sciences
|May 27, 2026
PubMed

Insights

Forkhead box O (FOXO) proteins have dual roles in digestive cancers, acting as tumor suppressors or oncoproteins. Understanding their switching mechanisms is key for developing targeted FOXO therapies in digestive system malignancies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Digestive system malignancies pose a significant global health burden.
  • Forkhead box O (FOXO) proteins are crucial transcriptional regulators involved in cell proliferation, apoptosis, and metabolism.
  • FOXO proteins exhibit context-dependent dual roles as tumor suppressors and oncoproteins in cancer.

Purpose of the Study:

  • To systematically review the molecular mechanisms behind FOXO functional switching in digestive system malignancies.
  • To explore therapeutic strategies targeting FOXO proteins in digestive cancers.
  • To provide a theoretical reference for precise intervention in digestive system tumors.

Main Methods:

  • Literature review focusing on molecular mechanisms of FOXO functional switching.
  • Analysis of FOXO roles across different tumor progression stages.
  • Examination of FOXO functions based on tumor-specific physiological properties.

Main Results:

  • FOXO's function switches spatiotemporally during tumor progression.
  • Distinct digestive system tumors exhibit unique FOXO-dependent physiological characteristics.
  • This functional duality presents challenges for FOXO-targeted cancer therapy.

Conclusions:

  • Understanding FOXO's dual roles and switching patterns is crucial for effective cancer therapy.
  • Targeted therapeutic strategies need to consider tumor stage and specific properties.
  • This review offers a framework for precise FOXO-based interventions in digestive malignancies.
Keywords:
FOXO familydigestive system tumorsspatiotemporal specificitytargeted therapy

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