Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Argentina; Instituto de Inmunología, Genética y Metabolismo, Facultad de Farmacia y Bioquímica, Hospital de Clínicas "José de San Martín", Caba, 1120, Argentina. Electronic address: [Email]
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.