LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton

LUZP1 is a centrosomal and actin cytoskeleton-localizing protein that regulates both ciliogenesis and actin filament bundling. As the cytoskeleton and cilia are implicated in metastasis and tumor suppression, we examined roles for LUZP1 in the context of cancer. Here we show that LUZP1 exhibits freq...

Descripción completa

Detalles Bibliográficos
Autores: Bozal Basterra, Laura, González Santamarta, María, Muratore, Veronica, Martín Martín, Natalia, Ercilla Eguiarte, Amaia, Rodríguez Pérez, José Antonio, Carracedo Pérez, Arkaitz, Sutherland, James D., Barrio Olano, María Rosa
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/51459
Acceso en línea:http://hdl.handle.net/10810/51459
Access Level:acceso abierto
Palabra clave:LUZP1
actin cytoskeleton
proliferation
migration
invasion
cancer
centrosome
id ES_8f577ddbb0807e62a906fb64f56fa796
oai_identifier_str oai:addi.ehu.eus:10810/51459
network_acronym_str ES
network_name_str España
repository_id_str
spelling LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin CytoskeletonBozal Basterra, LauraGonzález Santamarta, MaríaMuratore, VeronicaMartín Martín, NataliaErcilla Eguiarte, AmaiaRodríguez Pérez, José AntonioCarracedo Pérez, ArkaitzSutherland, James D.Barrio Olano, María RosaLUZP1actin cytoskeletonproliferationmigrationinvasioncancercentrosomeLUZP1 is a centrosomal and actin cytoskeleton-localizing protein that regulates both ciliogenesis and actin filament bundling. As the cytoskeleton and cilia are implicated in metastasis and tumor suppression, we examined roles for LUZP1 in the context of cancer. Here we show that LUZP1 exhibits frequent genomic aberrations in cancer, with a predominance of gene deletions. Furthermore, we demonstrate that CRISPR/Cas9-mediated loss of Luzp1 in mouse fibroblasts promotes cell migration and invasion features, reduces cell viability, and increases cell apoptosis, centriole numbers, and nuclear size while altering the actin cytoskeleton. Loss of Luzp1 also induced changes to ACTR3 (Actin Related Protein 3, also known as ARP3) and phospho-cofilin ratios, suggesting regulatory roles in actin polymerization, beyond its role in filament bundling. Our results point to an unprecedented role for LUZP1 in the regulation of cancer features through the control of actin cytoskeleton.We are grateful to the Fundacion Inocente, Inocente for their support. We also acknowledge funding by the grants BFU2017-84653-P (MINECO/FEDER, EU), SEV-2016-0644 (Severo Ochoa Excellence Program), 765445-EU (UbiCODE Program), SAF2017-90900-REDT (UBIRed Program), and IT1165-19 (Basque Country Government). Additional support was provided by the Department of Industry, Tourism, and Trade of the Basque Country Government (Elkartek Research Programs) and by the Innovation Technology Department of the Bizkaia County. LB-B acknowledges POSTD19048BOZA (Fundacion Cientifica AECC). VM acknowledges PRE2018086230 (MINECO/FEDER, EU). AC acknowledges the Basque Department of education (IKERTALDE IT1106-16), the MCIU [PID2019-108787RB-I00 (FEDER/EU)], the AECC (IDEAS175CARR; GCTRA18006CARR), La Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR17/and the European Research Council (Starting Grant 336343, PoC 754627, Consolidator grant 819242). CIBERONC was co-funded with FEDER funds. We are also grateful to Maria Vivanco's lab for providing reagents.Frontiers MediaEuropean Commission202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/51459reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MICINN/BFU2017-84653-P/info:eu-repo/grantAgreement/MICINN/PRE2018-086230/info:eu-repo/grantAgreement/MICINN/SEV-2016-0644/info:eu-repo/grantAgreement/EC/H2020/765445info:eu-repo/grantAgreement/MICINN/PID2019-108787RB-I00/info:eu-repo/grantAgreement/EC/FP7/336343info:eu-repo/grantAgreement/EC/H2020/754627info:eu-repo/grantAgreement/EC/H2020/819242https://www.frontiersin.org/articles/10.3389/fcell.2021.624089/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)Atribución 3.0 Españaoai:addi.ehu.eus:10810/514592026-06-18T09:23:17Z
dc.title.none.fl_str_mv LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
title LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
spellingShingle LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
Bozal Basterra, Laura
LUZP1
actin cytoskeleton
proliferation
migration
invasion
cancer
centrosome
title_short LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
title_full LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
title_fullStr LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
title_full_unstemmed LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
title_sort LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton
dc.creator.none.fl_str_mv Bozal Basterra, Laura
González Santamarta, María
Muratore, Veronica
Martín Martín, Natalia
Ercilla Eguiarte, Amaia
Rodríguez Pérez, José Antonio
Carracedo Pérez, Arkaitz
Sutherland, James D.
Barrio Olano, María Rosa
author Bozal Basterra, Laura
author_facet Bozal Basterra, Laura
González Santamarta, María
Muratore, Veronica
Martín Martín, Natalia
Ercilla Eguiarte, Amaia
Rodríguez Pérez, José Antonio
Carracedo Pérez, Arkaitz
Sutherland, James D.
Barrio Olano, María Rosa
author_role author
author2 González Santamarta, María
Muratore, Veronica
Martín Martín, Natalia
Ercilla Eguiarte, Amaia
Rodríguez Pérez, José Antonio
Carracedo Pérez, Arkaitz
Sutherland, James D.
Barrio Olano, María Rosa
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
dc.subject.none.fl_str_mv LUZP1
actin cytoskeleton
proliferation
migration
invasion
cancer
centrosome
topic LUZP1
actin cytoskeleton
proliferation
migration
invasion
cancer
centrosome
description LUZP1 is a centrosomal and actin cytoskeleton-localizing protein that regulates both ciliogenesis and actin filament bundling. As the cytoskeleton and cilia are implicated in metastasis and tumor suppression, we examined roles for LUZP1 in the context of cancer. Here we show that LUZP1 exhibits frequent genomic aberrations in cancer, with a predominance of gene deletions. Furthermore, we demonstrate that CRISPR/Cas9-mediated loss of Luzp1 in mouse fibroblasts promotes cell migration and invasion features, reduces cell viability, and increases cell apoptosis, centriole numbers, and nuclear size while altering the actin cytoskeleton. Loss of Luzp1 also induced changes to ACTR3 (Actin Related Protein 3, also known as ARP3) and phospho-cofilin ratios, suggesting regulatory roles in actin polymerization, beyond its role in filament bundling. Our results point to an unprecedented role for LUZP1 in the regulation of cancer features through the control of actin cytoskeleton.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/51459
url http://hdl.handle.net/10810/51459
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN/BFU2017-84653-P/
info:eu-repo/grantAgreement/MICINN/PRE2018-086230/
info:eu-repo/grantAgreement/MICINN/SEV-2016-0644/
info:eu-repo/grantAgreement/EC/H2020/765445
info:eu-repo/grantAgreement/MICINN/PID2019-108787RB-I00/
info:eu-repo/grantAgreement/EC/FP7/336343
info:eu-repo/grantAgreement/EC/H2020/754627
info:eu-repo/grantAgreement/EC/H2020/819242
https://www.frontiersin.org/articles/10.3389/fcell.2021.624089/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869413203747799040
score 15,300719

Similares en LA Referencia