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FOXO1 functions in the regulation of nicotinamide phosphoribosyltransferase (Nampt) expression

Bora Jeong1, Jeong Woo Park1, Jae Geun Kim2

  • 1Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, 44610, South Korea.

Biochemical and Biophysical Research Communications
|February 26, 2019
PubMed

Insights

Forkhead Box O1 (FOXO1), a tumor suppressor, directly inhibits nicotinamide phosphoribosyltransferase (Nampt) expression in breast cancer cells. This regulation impacts cell survival and proliferation, highlighting FOXO1

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Nicotinamide phosphoribosyltransferase (Nampt) is crucial for tumorigenesis, regulating cell growth, survival, DNA repair, and angiogenesis.
  • Forkhead Box O1 (FOXO1) is a known tumor suppressor protein implicated in various cellular processes.

Purpose of the Study:

  • To investigate the regulatory role of FOXO1 in Nampt expression within human breast cancer MCF-7 cells.
  • To elucidate the mechanism by which FOXO1 influences Nampt expression and its downstream effects.

Main Methods:

  • Analysis of FOXO1 binding to the 5'-flanking region of the nampt gene.
  • Investigating the impact of insulin and phosphatidylinositol 3-kinase (PI3K)/Akt signaling on Nampt expression.
  • Evaluating the effect of FOXO1 overexpression on insulin signaling-induced cell proliferation and survival.

Main Results:

  • FOXO1 directly binds to the 5'-flanking region of the nampt gene, inhibiting its expression.
  • Insulin and PI3K/Akt signaling increase Nampt expression, an effect suppressed by FOXO1.
  • FOXO1 overexpression counteracts insulin-induced cell survival and proliferation in MCF-7 cells.

Conclusions:

  • FOXO1 acts as a direct inhibitor of Nampt gene expression in human breast cancer cells.
  • FOXO1 plays a significant role in modulating Nampt-dependent pathways involved in cancer cell growth and survival.
  • Targeting the FOXO1-Nampt interaction could offer a therapeutic strategy for breast cancer.
Keywords:
Breast cancerCell viabilityForkhead Box O1Nicotinamide phosphoribosyltransferaseTranscriptional regulation

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