The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth

Detalhes bibliográficos
Autor(a) principal: Badenes, Marina
Data de Publicação: 2023
Outros Autores: Burbridge, Emma, Oikonomidi, Ioanna, Amin, Abdulbasit, de Carvalho, Érika, Kosack, Lindsay, Mariano, Camila, Domingos, Pedro, Faísca, Pedro, Adrain, Colin
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/158548
Resumo: Funding Information: The authors thank the Animal Facility, the Histopathology, the Advanced Imaging, and Flow cytometry units and the antibody service of the Instituto Gulbenkian de Ciência. We thank Cristina Branco for reagents and Sarah Maguire for advice about expression correlation analysis. We thank Colin Crump (Cambridge, UK) for providing the HSV-1 DNA. We thank Stefan Rose-John and Cristina Branco for advice concerning the LLC cell model and helpful discussions. We acknowledge the support of Fundação Calouste Gulbenkian; Queen’s University Belfast; Worldwide Cancer Research (14–1289); a Marie Curie Career Integration Grant (project no. 618769); and Fundação para aCiência e Tecnologica (FCT) (grants SFRH/BCC/52507/2014, PTDC/BEX-BCM/ 3015/2014, and LISBOA-01–0145-FEDER-031330), and funding from “La Caixa” Foundation under the agreement (LCF/PR/HR17/52150018). This work was developed with the support of the research infrastructure Congento, project LISBOA-01–0145-FEDER-022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and Foundation for Science and Technology (Portugal). Publisher Copyright: © 2023 Badenes et al.
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spelling The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growthEcologyBiochemistry, Genetics and Molecular Biology (miscellaneous)Plant ScienceHealth, Toxicology and MutagenesisSDG 3 - Good Health and Well-beingFunding Information: The authors thank the Animal Facility, the Histopathology, the Advanced Imaging, and Flow cytometry units and the antibody service of the Instituto Gulbenkian de Ciência. We thank Cristina Branco for reagents and Sarah Maguire for advice about expression correlation analysis. We thank Colin Crump (Cambridge, UK) for providing the HSV-1 DNA. We thank Stefan Rose-John and Cristina Branco for advice concerning the LLC cell model and helpful discussions. We acknowledge the support of Fundação Calouste Gulbenkian; Queen’s University Belfast; Worldwide Cancer Research (14–1289); a Marie Curie Career Integration Grant (project no. 618769); and Fundação para aCiência e Tecnologica (FCT) (grants SFRH/BCC/52507/2014, PTDC/BEX-BCM/ 3015/2014, and LISBOA-01–0145-FEDER-031330), and funding from “La Caixa” Foundation under the agreement (LCF/PR/HR17/52150018). This work was developed with the support of the research infrastructure Congento, project LISBOA-01–0145-FEDER-022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and Foundation for Science and Technology (Portugal). Publisher Copyright: © 2023 Badenes et al.The metalloprotease ADAM17 is a sheddase of key molecules, including TNF and epidermal growth factor receptor ligands. ADAM17 exists within an assemblage, the “sheddase complex,” containing a rhomboid pseudoprotease (iRhom1 or iRhom2). iRhoms control multiple aspects of ADAM17 biology. The FERM domain–containing protein iTAP/Frmd8 is an iRhom-binding protein that prevents the precocious shunting of ADAM17 and iRhom2 to lysosomes and their consequent degradation. As pathophysiological role(s) of iTAP/Frmd8 have not been addressed, we characterized the impact of iTAP/Frmd8 loss on ADAM17-associated phenotypes in mice. We show that iTAP/Frmd8 KO mice exhibit defects in inflammatory and intestinal epithelial barrier repair functions, but not the collateral defects associated with global ADAM17 loss. Furthermore, we show that iTAP/Frmd8 regulates cancer cell growth in a cell-autonomous manner and by modulating the tumor microenvironment. Our work suggests that pharmacological intervention at the level of iTAP/Frmd8 may be beneficial to target ADAM17 activity in specific compartments during chronic inflammatory diseases or cancer, while avoiding the collateral impact on the vital functions associated with the widespread inhibition of ADAM17.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNBadenes, MarinaBurbridge, EmmaOikonomidi, IoannaAmin, Abdulbasitde Carvalho, ÉrikaKosack, LindsayMariano, CamilaDomingos, PedroFaísca, PedroAdrain, Colin2023-09-30T22:22:10Z2023-042023-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/158548eng2575-1077PURE: 72694737https://doi.org/10.26508/lsa.202201644info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:41:06Zoai:run.unl.pt:10362/158548Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:57:12.507839Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
title The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
spellingShingle The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
Badenes, Marina
Ecology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Plant Science
Health, Toxicology and Mutagenesis
SDG 3 - Good Health and Well-being
title_short The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
title_full The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
title_fullStr The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
title_full_unstemmed The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
title_sort The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth
author Badenes, Marina
author_facet Badenes, Marina
Burbridge, Emma
Oikonomidi, Ioanna
Amin, Abdulbasit
de Carvalho, Érika
Kosack, Lindsay
Mariano, Camila
Domingos, Pedro
Faísca, Pedro
Adrain, Colin
author_role author
author2 Burbridge, Emma
Oikonomidi, Ioanna
Amin, Abdulbasit
de Carvalho, Érika
Kosack, Lindsay
Mariano, Camila
Domingos, Pedro
Faísca, Pedro
Adrain, Colin
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Badenes, Marina
Burbridge, Emma
Oikonomidi, Ioanna
Amin, Abdulbasit
de Carvalho, Érika
Kosack, Lindsay
Mariano, Camila
Domingos, Pedro
Faísca, Pedro
Adrain, Colin
dc.subject.por.fl_str_mv Ecology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Plant Science
Health, Toxicology and Mutagenesis
SDG 3 - Good Health and Well-being
topic Ecology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Plant Science
Health, Toxicology and Mutagenesis
SDG 3 - Good Health and Well-being
description Funding Information: The authors thank the Animal Facility, the Histopathology, the Advanced Imaging, and Flow cytometry units and the antibody service of the Instituto Gulbenkian de Ciência. We thank Cristina Branco for reagents and Sarah Maguire for advice about expression correlation analysis. We thank Colin Crump (Cambridge, UK) for providing the HSV-1 DNA. We thank Stefan Rose-John and Cristina Branco for advice concerning the LLC cell model and helpful discussions. We acknowledge the support of Fundação Calouste Gulbenkian; Queen’s University Belfast; Worldwide Cancer Research (14–1289); a Marie Curie Career Integration Grant (project no. 618769); and Fundação para aCiência e Tecnologica (FCT) (grants SFRH/BCC/52507/2014, PTDC/BEX-BCM/ 3015/2014, and LISBOA-01–0145-FEDER-031330), and funding from “La Caixa” Foundation under the agreement (LCF/PR/HR17/52150018). This work was developed with the support of the research infrastructure Congento, project LISBOA-01–0145-FEDER-022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and Foundation for Science and Technology (Portugal). Publisher Copyright: © 2023 Badenes et al.
publishDate 2023
dc.date.none.fl_str_mv 2023-09-30T22:22:10Z
2023-04
2023-04-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/158548
url http://hdl.handle.net/10362/158548
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2575-1077
PURE: 72694737
https://doi.org/10.26508/lsa.202201644
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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