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

AMABLE G; MARTINEZ-LEON EDUARDO; PICCO M E; 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 epidemiologicstudies have revealed strong inverse associations between metformin use and risk of colorectal cancer development. Nevertheless, the underlying mechanisms are still uncertain.  The Wnt/b-catenin pathway, whichplays a central role in intestinal homeostasis and sporadic colorectal cancerdevelopment, is regulated by phosphorylation cascades that are dependent andindependent of Wnt. Here we report that a non-canonical Ser552phosphorylation in b-catenin, which promotesits nuclear accumulation and transcriptional activity, is blocked by metformin viaAMPK-mediated PI3K/Aktsignaling inhibition.<!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:"ＭＳ 明朝";mso-font-charset:78;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:1 134676480 16 0 131072 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0in;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman";}span.highlight{mso-style-name:highlight;mso-style-unhide:no;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:JA;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:10.0pt;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.25in 1.0in 1.25in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->