INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
artículos
Título:
Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
Autor/es:
MARTINEZ-LEON EDUARDO; PICCO M E; ENRIQUE ROZENGURT; REY O; AMABLE G; NEMIROVSKY S I
Revista:
JOURNAL OF CELLULAR PHYSIOLOGY
Editorial:
Wiley-Liss Inc.info@wiley.com
Referencias:
Año: 2020 vol. 235 p. 8334 - 8344
ISSN:
0021-9541
Resumen:
E-cadherin, acentral component of the adherens junction (Aj), is a single-pass transmembraneprotein that mediates cell-cell adhesion. The loss of E-cadherin surface expression, and therefore cell-celladhesion, leads to increased cell migration and invasion.  Treatment of colorectal (CRC)-derivedcells (SW-480, HT-29) with 2 mMmetformin promoted a redistribution of cytosolic E-cadherin to de novo formed puncta along the lengthof the contacting membranes of these cells. Metformin also promoted translocation fromthe cytosol to the plasma membrane of p120-catenin,another core component of the AJs. Furthermore, E-cadherin and p120-catenin co-localized with b-catenin at cell-cellcontacts.  Western blot analysis oflysates of CRC-derived cells revealed a substantial metformin-induced increase inthe level of p120-catenin as well as E-cadherin phosphorylation on Ser838/840,a modification associated to b-catenin/E-cadherin interaction.  Thesemodifications in E-cadherin, p120-catenin and b-catenin localization suggest that metformin induces rebuilding of AJsin CRC-derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase(FAK) as revealed by a significant decrease in the phosphorylation ofFAK at Tyr397and paxillin at Tyr118.  These changes were associated to a reductionin the numbers, but an increase in the size, of focal adhesions (FAs) and by the inhibition ofcell migration. Overall, these observations indicate that metformin targets multiplepathways associated to colorectal cancer development and progression.<!-- /* 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:3 0 0 0 1 0;}@font-face{font-family:"Avenir 45 Book";panose-1:0 0 0 0 0 0 0 0 0 0;mso-font-alt:"Times New Roman";mso-font-charset:77;mso-generic-font-family:swiss;mso-font-format:other;mso-font-pitch:auto;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-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-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;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;}size:612.0pt 792.0pt;margin:72.0pt 90.0pt 72.0pt 90.0pt;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}