Metformin inhibits β-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells.

Abstract

Several epidemiologic studies have revealed strong inverse associations between metformin use and risk of colorectal cancer development. Nevertheless, the underlying mechanisms are still uncertain. The Wnt/β-catenin pathway, which plays a central role in intestinal homeostasis and sporadic colorectal cancer development, is regulated by phosphorylation cascades that are dependent and independent of Wnt. Here we report that a non-canonical Ser552 phosphorylation in β-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by metformin via AMPK-mediated PI3K/Akt signaling inhibition.

• Authors: Gastón Amable, Eduardo Martínez-León, María Elisa Picco, Nicolas Di Siervi, Carlos Davio, Enrique Rozengurt, Osvaldo Rey
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 112 Pg. 88-94 (07 2019) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 31082618 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• CTNNB1 protein, human
• beta Catenin
• Metformin
• Proto-Oncogene Proteins c-akt
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Cell Line
• Colorectal Neoplasms (metabolism, pathology)
• Humans
• Metformin (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• beta Catenin (metabolism)