Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis

Adhesion to the extracellular matrix (ECM) is required for normal epithelial cell survival. Disruption of this interaction leads to a specific type of apoptosis known as anoikis. Yet, there are physiological and pathological situations in which cells not connected to the ECM are protected from anoik...

Descripción completa

Detalles Bibliográficos
Autores: Valencia Expósito, Andrea, Gómez Lamarca, Mª Jesús, Widmann, Thomas J., Martín Bermudo, María Dolores
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/135006
Acceso en línea:https://hdl.handle.net/11441/135006
https://doi.org/10.3389/fcell.2022.892691
Access Level:acceso abierto
Palabra clave:integrins
survival
JNK EGFR
oncogenesis
id ES_ce55a32bfceee2d4ce5b79c90e34005a
oai_identifier_str oai:idus.us.es:11441/135006
network_acronym_str ES
network_name_str España
repository_id_str
spelling Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and OncogenesisValencia Expósito, AndreaGómez Lamarca, Mª JesúsWidmann, Thomas J.Martín Bermudo, María DoloresintegrinssurvivalJNK EGFRoncogenesisAdhesion to the extracellular matrix (ECM) is required for normal epithelial cell survival. Disruption of this interaction leads to a specific type of apoptosis known as anoikis. Yet, there are physiological and pathological situations in which cells not connected to the ECM are protected from anoikis, such as during cell migration or metastasis. The main receptors transmitting signals from the ECM are members of the integrin family. However, although integrin-mediated cell-ECM anchorage has been long recognized as crucial for epithelial cell survival, the in vivo significance of this interaction remains to be weighed. In this work, we have used the Drosophila wing imaginal disc epithelium to analyze the importance of integrins as survival factors during epithelia morphogenesis. We show that reducing integrin expression in the wing disc induces caspase-dependent cell death and basal extrusion of the dead cells. In this case, anoikis is mediated by the activation of the JNK pathway, which in turn triggers expression of the proapoptotic protein Hid. In addition, our results strongly suggest that, during wing disc morphogenesis, the EGFR pathway protects cells undergoing cell shape changes upon ECM detachment from anoikis. Furthermore, we show that oncogenic activation of the EGFR/Ras pathway in integrin mutant cells rescues them from apoptosis while promoting their extrusion from the epithelium. Altogether, our results support the idea that integrins promote cell survival during normal tissue morphogenesis and prevent the extrusion of transformed cells.España MICINN (Nos. BFU2016-80797-R and PID2019-109013GB-100)MDPIBiología CelularMinisterio de Ciencia, Innovación y Universidades (MICINN). España2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/135006https://doi.org/10.3389/fcell.2022.892691reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésFrontiers in Cell and Developmental Biology, 10, 892691.BFU2016-80797-RPID2019-109013GB-100https://dx.doi.org/10.3389/fcell.2022.892691info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1350062026-06-17T12:51:07Z
dc.title.none.fl_str_mv Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
title Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
spellingShingle Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
Valencia Expósito, Andrea
integrins
survival
JNK EGFR
oncogenesis
title_short Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
title_full Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
title_fullStr Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
title_full_unstemmed Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
title_sort Integrins Cooperate With the EGFR/Ras Pathway to Preserve Epithelia Survival and Architecture in Development and Oncogenesis
dc.creator.none.fl_str_mv Valencia Expósito, Andrea
Gómez Lamarca, Mª Jesús
Widmann, Thomas J.
Martín Bermudo, María Dolores
author Valencia Expósito, Andrea
author_facet Valencia Expósito, Andrea
Gómez Lamarca, Mª Jesús
Widmann, Thomas J.
Martín Bermudo, María Dolores
author_role author
author2 Gómez Lamarca, Mª Jesús
Widmann, Thomas J.
Martín Bermudo, María Dolores
author2_role author
author
author
dc.contributor.none.fl_str_mv Biología Celular
Ministerio de Ciencia, Innovación y Universidades (MICINN). España
dc.subject.none.fl_str_mv integrins
survival
JNK EGFR
oncogenesis
topic integrins
survival
JNK EGFR
oncogenesis
description Adhesion to the extracellular matrix (ECM) is required for normal epithelial cell survival. Disruption of this interaction leads to a specific type of apoptosis known as anoikis. Yet, there are physiological and pathological situations in which cells not connected to the ECM are protected from anoikis, such as during cell migration or metastasis. The main receptors transmitting signals from the ECM are members of the integrin family. However, although integrin-mediated cell-ECM anchorage has been long recognized as crucial for epithelial cell survival, the in vivo significance of this interaction remains to be weighed. In this work, we have used the Drosophila wing imaginal disc epithelium to analyze the importance of integrins as survival factors during epithelia morphogenesis. We show that reducing integrin expression in the wing disc induces caspase-dependent cell death and basal extrusion of the dead cells. In this case, anoikis is mediated by the activation of the JNK pathway, which in turn triggers expression of the proapoptotic protein Hid. In addition, our results strongly suggest that, during wing disc morphogenesis, the EGFR pathway protects cells undergoing cell shape changes upon ECM detachment from anoikis. Furthermore, we show that oncogenic activation of the EGFR/Ras pathway in integrin mutant cells rescues them from apoptosis while promoting their extrusion from the epithelium. Altogether, our results support the idea that integrins promote cell survival during normal tissue morphogenesis and prevent the extrusion of transformed cells.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/135006
https://doi.org/10.3389/fcell.2022.892691
url https://hdl.handle.net/11441/135006
https://doi.org/10.3389/fcell.2022.892691
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Frontiers in Cell and Developmental Biology, 10, 892691.
BFU2016-80797-R
PID2019-109013GB-100
https://dx.doi.org/10.3389/fcell.2022.892691
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419982051344384
score 15,300724

Similares en LA Referencia