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

  • Authors:
    • Song Yi Park
    • Dasarang Kim
    • Sun‑Ho Kee

  • View Affiliations

  • Published online on: January 4, 2019     https://doi.org/10.3892/ol.2019.9892
  • Pages: 2695-2702

  • Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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March-2019
Volume 17 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
  • SCImago Journal Rank (SJR): 0.644
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Spandidos Publications style
Park SY, Kim D and Kee SH: Metformin‑activated AMPK regulates β‑catenin to reduce cell proliferation in colon carcinoma RKO cells. Oncol Lett 17: 2695-2702, 2019.
APA
Park, S.Y., Kim, D., & Kee, S. (2019). Metformin‑activated AMPK regulates β‑catenin to reduce cell proliferation in colon carcinoma RKO cells. Oncology Letters, 17, 2695-2702. https://doi.org/10.3892/ol.2019.9892
MLA
Park, S. Y., Kim, D., Kee, S."Metformin‑activated AMPK regulates β‑catenin to reduce cell proliferation in colon carcinoma RKO cells". Oncology Letters 17.3 (2019): 2695-2702.
Chicago
Park, S. Y., Kim, D., Kee, S."Metformin‑activated AMPK regulates β‑catenin to reduce cell proliferation in colon carcinoma RKO cells". Oncology Letters 17, no. 3 (2019): 2695-2702. https://doi.org/10.3892/ol.2019.9892