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FOXO family in regulating cancer and metabolism

Jian Ma1, Smita Matkar2, Xin He2

  • 1Department of Cancer Biology, Abramson Family Cancer Research Institute, Abramson Cancer Center, Institute of Diabetes, Obesity, and Metabolism (IDOM), University of Pennsylvania Perelman School of Medicine, 421 Curie Blvd., Philadelphia, PA 19104, USA; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 678 Haping Road, Harbin, Heilongjiang 150069, China; College of Life Science, Northeast Forestry University, 26 Hexing Road, Harbin, Heilongjiang 150040, China.

Seminars in Cancer Biology
|February 8, 2018
PubMed

Insights

Forkhead box (FOX) proteins, known as FOXOs, regulate cell metabolism and tumorigenesis. This review explores their paradoxical roles in cancer, focusing on PI3K/AKT pathway interactions and metabolic crosstalk.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Forkhead box (FOX) proteins, specifically FOXO transcription factors (TFs), regulate diverse biological processes.
  • These include development, cell signaling, tumorigenesis, and cell metabolism.
  • Dysregulation of FOXO function is implicated in various diseases, particularly cancer.

Purpose of the Study:

  • To review the multifaceted roles of FOXO proteins in cancer regulation and metabolism.
  • To examine the influence of pathway crosstalk on FOXO function.
  • To discuss the paradoxical roles of FOXOs in cancer cell fate, including drug resistance/sensitivity to PI3K/AKT inhibitors.

Main Methods:

  • Literature review and synthesis of existing research on FOXO proteins.
  • Analysis of signaling pathways and their interactions with FOXOs.
  • Focus on the interplay between cancer pathways and cell metabolism.

Main Results:

  • FOXO proteins are critical regulators of both tumor progression and cell metabolism.
  • Crosstalk among signaling pathways significantly modulates FOXO activity.
  • FOXO proteins exhibit paradoxical effects on cancer, influencing sensitivity and resistance to targeted therapies like PI3K/AKT inhibitors.

Conclusions:

  • FOXO-mediated crosstalk between cancer and metabolic pathways critically impacts cancer outcomes.
  • Understanding these complex interactions is essential for developing novel cancer therapies.
  • Targeting FOXO pathways may offer new strategies for overcoming drug resistance in cancer treatment.
Keywords:
AKTCancerFOXOMetabolismPKA

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