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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/110692
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:37:22Zoai: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:34982025-09-29 09:37:22.509CONICET 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/ |
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application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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