Metformin-activated AMPK regulates β-catenin to reduce cell proliferation in colon carcinoma RKO cells

Song Yi Park, Dasarang Kim, Sun-Ho Kee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Metformin can suppress cell proliferation and viability by altering mitochondrial energy metabolism and by the activation of 5'-adenosine monophosphate-activated protein kinase (AMPK). The current study demonstrated that metformin-induced suppression of cell proliferation is further potentiated by AMPK-mediated suppression of β-catenin-dependent wingless-type (Wnt) signaling. Treatment with metformin reduced mitochondrial oxidative phosphorylation and glycolysis, leading to an energy imbalance that may induce AMPK phosphorylation in RKO cells. Metformin treatment also decreased β-catenin expression in the cytoplasm and nucleus. Active AMPK was revealed to be associated with β-catenin. The decrease in β-catenin expression was inhibited by proteosome inhibition through phosphorylation of β-catenin at serine 33/37. Given that nuclear translocation-associated phosphorylation of β-catenin at serine was maintained, the association of β-catenin with AMPK may sequester β-catenin in the cytoplasm and lead to proteosomal degradation. Furthermore, metformin-induced suppression of cell proliferation was partially recovered by AMPK inhibition, while metformin inhibited Wnt-mediated cell proliferation and β-catenin expression. The present results suggest that AMPK activation can suppress β-catenin-dependent Wnt signaling by cytoplasmic sequestering of β-catenin through AMPK, which further decreases cell proliferation in addition to metformin-induced mitochondrial dysfunction.

Original languageEnglish
Pages (from-to)2695-2702
Number of pages8
JournalOncology Letters
Volume17
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

Fingerprint

Catenins
Metformin
Adenosine Monophosphate
Protein Kinases
Colon
Cell Proliferation
Carcinoma
Phosphorylation
Serine
Cytoplasm
Oxidative Phosphorylation
Glycolysis
Energy Metabolism
Cell Survival

Keywords

  • 5'-adenosine monophosphate-activated protein kinase
  • Adenosine 5'-triphosphate production
  • Cell proliferation
  • Metformin
  • β-catenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Metformin-activated AMPK regulates β-catenin to reduce cell proliferation in colon carcinoma RKO cells. / Park, Song Yi; Kim, Dasarang; Kee, Sun-Ho.

In: Oncology Letters, Vol. 17, No. 3, 01.03.2019, p. 2695-2702.

Research output: Contribution to journalArticle

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