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

AMABLE, GASTÓN; MARTÍNEZ-LEÓN, EDUARDO; PICCO, MARÍA ELISA; DI SIERVI, NICOLAS; DAVIO, CARLOS; ROZENGURT, ENRIQUE; REY, OSVALDO

INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELLULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2019 vol. 112 p. 88 - 94

1357-2725

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.