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Adiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription

Jing Liu1, Janice B B Lam, Kim H M Chow

  • 1Department of Pharmacology, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong, China.

Carcinogenesis
|August 15, 2008
PubMed

Insights

Adiponectin (ADN) promotes Wnt inhibitory factor-1 (WIF1) expression, inhibiting breast cancer cell growth. ADN reduces WIF1 promoter methylation by downregulating Sp1 and DNMT1, suggesting a novel anticancer mechanism.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Adiponectin (ADN) exhibits anti-cancer properties by inhibiting growth.
  • Previous studies showed ADN impedes Wnt/beta-catenin signaling in breast cancer cells.
  • Wnt inhibitory factor-1 (WIF1), a Wnt antagonist, is frequently silenced in breast tumors.

Purpose of the Study:

  • To investigate the effect of ADN on WIF1 expression in breast cancer.
  • To elucidate the mechanism by which ADN regulates WIF1.
  • To explore the role of WIF1 in ADN's anti-cancer activity.

Main Methods:

  • MDA-MB-231 cells were treated with ADN to assess WIF1 gene and protein expression.
  • WIF1 overexpression and knockdown experiments were performed.
  • In vivo studies involved recombinant ADN and adenovirus-mediated overexpression in tumor models.
  • CpG island methylation, Sp1, and DNMT1 levels were analyzed.

Main Results:

  • ADN time-dependently stimulated WIF1 gene and protein expression in MDA-MB-231 cells.
  • WIF1 overexpression mimicked ADN's inhibitory effects on cell proliferation and Wnt signaling.
  • ADN treatment reduced WIF1 promoter methylation by decreasing Sp1 and DNMT1 levels.
  • In vivo, ADN enhanced WIF1 expression in tumors and inhibited tumor growth.

Conclusions:

  • Adiponectin (ADN) promotes Wnt inhibitory factor-1 (WIF1) expression in breast cancer cells.
  • ADN's mechanism involves reducing WIF1 promoter methylation via Sp1 and DNMT1 downregulation.
  • These findings suggest ADN exerts anti-tumor effects partly by upregulating WIF1.

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