Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation

Autores
Amable, Gastón Federico; Martínez León, Eduardo Antonio; Picco, María Elisa; Nemirovsky, Sergio Ivan; Rozengurt, Enrique; Rey, Osvaldo
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
E‐cadherin, a central component of the adherens junction (AJ), is a single‐pass trans- membrane protein that mediates cell?cell adhesion. The loss of E‐cadherin surface ex- pression, and therefore cell?cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)‐derived cells (SW‐480 and HT‐29) with 2.0 mM metformin promoted a redistribution of cytosolic E‐cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120‐catenin, another core component of the AJs. Furthermore, E‐cadherin and p120‐catenin colocalized with β‐catenin at cell?cell contacts. Western blot analysis of lysates of CRC‐derived cells revealed a substantial metformin‐induced increase in the level of p120‐catenin as well as E‐cadherin phosphorylation on Ser838/840, a modification associated with β‐catenin/ E‐cadherin interaction. These modifications in E‐cadherin, p120‐catenin and β‐catenin localization suggest that metformin induces rebuilding of AJs in CRC‐derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118. These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression.
Fil: Amable, Gastón Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Martínez León, Eduardo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Picco, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Nemirovsky, Sergio Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Rozengurt, Enrique. University of California at Los Angeles; Estados Unidos
Fil: Rey, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Materia
COLORECTAL CANCER
E-CADHERIN
FAK
METFORMIN
B-CATENIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/110692
Acceder
id CONICETDig_e97ec325743423aba24027727968afcd
oai_identifier_str oai:ri.conicet.gov.ar:11336/110692
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulationAmable, Gastón FedericoMartínez León, Eduardo AntonioPicco, María ElisaNemirovsky, Sergio IvanRozengurt, EnriqueRey, OsvaldoCOLORECTAL CANCERE-CADHERINFAKMETFORMINB-CATENINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1E‐cadherin, a central component of the adherens junction (AJ), is a single‐pass trans- membrane protein that mediates cell?cell adhesion. The loss of E‐cadherin surface ex- pression, and therefore cell?cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)‐derived cells (SW‐480 and HT‐29) with 2.0 mM metformin promoted a redistribution of cytosolic E‐cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120‐catenin, another core component of the AJs. Furthermore, E‐cadherin and p120‐catenin colocalized with β‐catenin at cell?cell contacts. Western blot analysis of lysates of CRC‐derived cells revealed a substantial metformin‐induced increase in the level of p120‐catenin as well as E‐cadherin phosphorylation on Ser838/840, a modification associated with β‐catenin/ E‐cadherin interaction. These modifications in E‐cadherin, p120‐catenin and β‐catenin localization suggest that metformin induces rebuilding of AJs in CRC‐derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118. These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression.Fil: Amable, Gastón Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Martínez León, Eduardo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Picco, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Nemirovsky, Sergio Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rozengurt, Enrique. University of California at Los Angeles; Estados UnidosFil: Rey, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaWiley2020-04-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/110692Amable, Gastón Federico; Martínez León, Eduardo Antonio; Picco, María Elisa; Nemirovsky, Sergio Ivan; Rozengurt, Enrique; et al.; Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation; Wiley; Journal of Cellular Physiology; 2-4-2020; 1-110021-9541CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29677info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.29677info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:26:19Zoai:ri.conicet.gov.ar:11336/110692instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:26:20.013CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
title Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
spellingShingle Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
Amable, Gastón Federico
COLORECTAL CANCER
E-CADHERIN
FAK
METFORMIN
B-CATENIN
title_short Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
title_full Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
title_fullStr Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
title_full_unstemmed Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
title_sort Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
dc.creator.none.fl_str_mv Amable, Gastón Federico
Martínez León, Eduardo Antonio
Picco, María Elisa
Nemirovsky, Sergio Ivan
Rozengurt, Enrique
Rey, Osvaldo
author Amable, Gastón Federico
author_facet Amable, Gastón Federico
Martínez León, Eduardo Antonio
Picco, María Elisa
Nemirovsky, Sergio Ivan
Rozengurt, Enrique
Rey, Osvaldo
author_role author
author2 Martínez León, Eduardo Antonio
Picco, María Elisa
Nemirovsky, Sergio Ivan
Rozengurt, Enrique
Rey, Osvaldo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv COLORECTAL CANCER
E-CADHERIN
FAK
METFORMIN
B-CATENIN
topic COLORECTAL CANCER
E-CADHERIN
FAK
METFORMIN
B-CATENIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv E‐cadherin, a central component of the adherens junction (AJ), is a single‐pass trans- membrane protein that mediates cell?cell adhesion. The loss of E‐cadherin surface ex- pression, and therefore cell?cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)‐derived cells (SW‐480 and HT‐29) with 2.0 mM metformin promoted a redistribution of cytosolic E‐cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120‐catenin, another core component of the AJs. Furthermore, E‐cadherin and p120‐catenin colocalized with β‐catenin at cell?cell contacts. Western blot analysis of lysates of CRC‐derived cells revealed a substantial metformin‐induced increase in the level of p120‐catenin as well as E‐cadherin phosphorylation on Ser838/840, a modification associated with β‐catenin/ E‐cadherin interaction. These modifications in E‐cadherin, p120‐catenin and β‐catenin localization suggest that metformin induces rebuilding of AJs in CRC‐derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118. These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression.
Fil: Amable, Gastón Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Martínez León, Eduardo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Picco, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Nemirovsky, Sergio Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Rozengurt, Enrique. University of California at Los Angeles; Estados Unidos
Fil: Rey, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
description E‐cadherin, a central component of the adherens junction (AJ), is a single‐pass trans- membrane protein that mediates cell?cell adhesion. The loss of E‐cadherin surface ex- pression, and therefore cell?cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)‐derived cells (SW‐480 and HT‐29) with 2.0 mM metformin promoted a redistribution of cytosolic E‐cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120‐catenin, another core component of the AJs. Furthermore, E‐cadherin and p120‐catenin colocalized with β‐catenin at cell?cell contacts. Western blot analysis of lysates of CRC‐derived cells revealed a substantial metformin‐induced increase in the level of p120‐catenin as well as E‐cadherin phosphorylation on Ser838/840, a modification associated with β‐catenin/ E‐cadherin interaction. These modifications in E‐cadherin, p120‐catenin and β‐catenin localization suggest that metformin induces rebuilding of AJs in CRC‐derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118. These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression.
publishDate 2020
dc.date.none.fl_str_mv 2020-04-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/110692
Amable, Gastón Federico; Martínez León, Eduardo Antonio; Picco, María Elisa; Nemirovsky, Sergio Ivan; Rozengurt, Enrique; et al.; Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation; Wiley; Journal of Cellular Physiology; 2-4-2020; 1-11
0021-9541
CONICET Digital
CONICET
url http://hdl.handle.net/11336/110692
identifier_str_mv Amable, Gastón Federico; Martínez León, Eduardo Antonio; Picco, María Elisa; Nemirovsky, Sergio Ivan; Rozengurt, Enrique; et al.; Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation; Wiley; Journal of Cellular Physiology; 2-4-2020; 1-11
0021-9541
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29677
info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.29677
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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