CRMP2 as a candidate target to interfere with lung cancer cell migration

Collapsin response mediator protein 2 (CRMP2) is an adaptor protein that adds tubulin dimers to the growing tip of a microtubule. First described in neurons, it is now considered a ubiquitous protein that intervenes in processes such as cytoskeletal remodeling, synaptic connection and trafficking of...

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Autores: Morales-Urteaga, X. (Xabier)|||/items/d0645dd3-b674-4c5d-a5d4-646870e4c006, Peláez, R. (Rafael)|||/items/6fbeb938-c1d9-48c3-9ca1-7bdcb0b1cdb4, Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713, Ortiz-de-Solorzano, C. (Carlos)|||/items/b2c0bd13-68a7-437c-b67f-2e5f1a9f0324, Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/62845
Acceso en línea:https://hdl.handle.net/10171/62845
Access Level:acceso abierto
Palabra clave:CRMP2
Lung cancer
Migration
Cytoskeleton
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spelling CRMP2 as a candidate target to interfere with lung cancer cell migrationMorales-Urteaga, X. (Xabier)|||/items/d0645dd3-b674-4c5d-a5d4-646870e4c006Peláez, R. (Rafael)|||/items/6fbeb938-c1d9-48c3-9ca1-7bdcb0b1cdb4Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713Ortiz-de-Solorzano, C. (Carlos)|||/items/b2c0bd13-68a7-437c-b67f-2e5f1a9f0324Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024CRMP2Lung cancerMigrationCytoskeletonCollapsin response mediator protein 2 (CRMP2) is an adaptor protein that adds tubulin dimers to the growing tip of a microtubule. First described in neurons, it is now considered a ubiquitous protein that intervenes in processes such as cytoskeletal remodeling, synaptic connection and trafficking of voltage channels. Mounting evidence supports that CRMP2 plays an essential role in neuropathology and, more recently, in cancer. We have previously described a positive correlation between nuclear phosphorylation of CRMP2 and poor prognosis in lung adenocarcinoma patients. In this work, we studied whether this cytoskeleton molding protein is involved in cancer cell migration. To this aim, we evaluated CRMP2 phosphorylation and localization in the extending lamella of lung adenocarcinoma migrating cells using in vitro assays and in vivo confocal microscopy. We demonstrated that constitutive phosphorylation of CRMP2 impaired lamella formation, cell adhesion and oriented migration. In search of a mechanistic explanation of this phenomenon, we discovered that CRMP2 Ser522 phospho-mimetic mutants display unstable tubulin polymers, unable to bind EB1 plus-Tip protein and the cortical actin adaptor IQGAP1. In addition, integrin recycling is defective and invasive structures are less evident in these mutants. Significantly, mouse xenograft tumors of NSCLC expressing CRMP2 phosphorylation mimetic mutants grew significantly less than wild-type tumors.Dadun. Depósito Académico Digital Universidad de Navarra20222022-01-2520212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/62845reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/628452026-06-21T12:47:57Z
dc.title.none.fl_str_mv CRMP2 as a candidate target to interfere with lung cancer cell migration
title CRMP2 as a candidate target to interfere with lung cancer cell migration
spellingShingle CRMP2 as a candidate target to interfere with lung cancer cell migration
Morales-Urteaga, X. (Xabier)|||/items/d0645dd3-b674-4c5d-a5d4-646870e4c006
CRMP2
Lung cancer
Migration
Cytoskeleton
title_short CRMP2 as a candidate target to interfere with lung cancer cell migration
title_full CRMP2 as a candidate target to interfere with lung cancer cell migration
title_fullStr CRMP2 as a candidate target to interfere with lung cancer cell migration
title_full_unstemmed CRMP2 as a candidate target to interfere with lung cancer cell migration
title_sort CRMP2 as a candidate target to interfere with lung cancer cell migration
dc.creator.none.fl_str_mv Morales-Urteaga, X. (Xabier)|||/items/d0645dd3-b674-4c5d-a5d4-646870e4c006
Peláez, R. (Rafael)|||/items/6fbeb938-c1d9-48c3-9ca1-7bdcb0b1cdb4
Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713
Ortiz-de-Solorzano, C. (Carlos)|||/items/b2c0bd13-68a7-437c-b67f-2e5f1a9f0324
Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
author Morales-Urteaga, X. (Xabier)|||/items/d0645dd3-b674-4c5d-a5d4-646870e4c006
author_facet Morales-Urteaga, X. (Xabier)|||/items/d0645dd3-b674-4c5d-a5d4-646870e4c006
Peláez, R. (Rafael)|||/items/6fbeb938-c1d9-48c3-9ca1-7bdcb0b1cdb4
Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713
Ortiz-de-Solorzano, C. (Carlos)|||/items/b2c0bd13-68a7-437c-b67f-2e5f1a9f0324
Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
author_role author
author2 Peláez, R. (Rafael)|||/items/6fbeb938-c1d9-48c3-9ca1-7bdcb0b1cdb4
Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713
Ortiz-de-Solorzano, C. (Carlos)|||/items/b2c0bd13-68a7-437c-b67f-2e5f1a9f0324
Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv CRMP2
Lung cancer
Migration
Cytoskeleton
topic CRMP2
Lung cancer
Migration
Cytoskeleton
description Collapsin response mediator protein 2 (CRMP2) is an adaptor protein that adds tubulin dimers to the growing tip of a microtubule. First described in neurons, it is now considered a ubiquitous protein that intervenes in processes such as cytoskeletal remodeling, synaptic connection and trafficking of voltage channels. Mounting evidence supports that CRMP2 plays an essential role in neuropathology and, more recently, in cancer. We have previously described a positive correlation between nuclear phosphorylation of CRMP2 and poor prognosis in lung adenocarcinoma patients. In this work, we studied whether this cytoskeleton molding protein is involved in cancer cell migration. To this aim, we evaluated CRMP2 phosphorylation and localization in the extending lamella of lung adenocarcinoma migrating cells using in vitro assays and in vivo confocal microscopy. We demonstrated that constitutive phosphorylation of CRMP2 impaired lamella formation, cell adhesion and oriented migration. In search of a mechanistic explanation of this phenomenon, we discovered that CRMP2 Ser522 phospho-mimetic mutants display unstable tubulin polymers, unable to bind EB1 plus-Tip protein and the cortical actin adaptor IQGAP1. In addition, integrin recycling is defective and invasive structures are less evident in these mutants. Significantly, mouse xenograft tumors of NSCLC expressing CRMP2 phosphorylation mimetic mutants grew significantly less than wild-type tumors.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
2022
2022-01-25
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/62845
url https://hdl.handle.net/10171/62845
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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