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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...

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Autores principales: Bozal-Basterra, Laura, Gonzalez-Santamarta, María, Muratore, Veronica, Martín-Martín, Natalia, Ercilla, Amaia, Rodríguez, Jose A., Carracedo, Arkaitz, Sutherland, James D., Barrio, Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049182/
https://www.ncbi.nlm.nih.gov/pubmed/33869174
http://dx.doi.org/10.3389/fcell.2021.624089
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author Bozal-Basterra, Laura
Gonzalez-Santamarta, María
Muratore, Veronica
Martín-Martín, Natalia
Ercilla, Amaia
Rodríguez, Jose A.
Carracedo, Arkaitz
Sutherland, James D.
Barrio, Rosa
author_facet Bozal-Basterra, Laura
Gonzalez-Santamarta, María
Muratore, Veronica
Martín-Martín, Natalia
Ercilla, Amaia
Rodríguez, Jose A.
Carracedo, Arkaitz
Sutherland, James D.
Barrio, Rosa
author_sort Bozal-Basterra, Laura
collection PubMed
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.
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spelling pubmed-80491822021-04-16 LUZP1 Controls Cell Division, Migration and Invasion Through Regulation of the Actin Cytoskeleton Bozal-Basterra, Laura Gonzalez-Santamarta, María Muratore, Veronica Martín-Martín, Natalia Ercilla, Amaia Rodríguez, Jose A. Carracedo, Arkaitz Sutherland, James D. Barrio, Rosa Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-04-01 /pmc/articles/PMC8049182/ /pubmed/33869174 http://dx.doi.org/10.3389/fcell.2021.624089 Text en Copyright © 2021 Bozal-Basterra, Gonzalez-Santamarta, Muratore, Martín-Martín, Ercilla, Rodríguez, Carracedo, Sutherland and Barrio. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Bozal-Basterra, Laura
Gonzalez-Santamarta, María
Muratore, Veronica
Martín-Martín, Natalia
Ercilla, Amaia
Rodríguez, Jose A.
Carracedo, Arkaitz
Sutherland, James D.
Barrio, Rosa
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
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_short 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
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049182/
https://www.ncbi.nlm.nih.gov/pubmed/33869174
http://dx.doi.org/10.3389/fcell.2021.624089
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