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

被引:13
作者
Bozal-Basterra, Laura [1 ]
Gonzalez-Santamarta, Maria [1 ,6 ]
Muratore, Veronica [1 ]
Martin-Martin, Natalia [1 ]
Ercilla, Amaia [1 ,2 ]
Rodriguez, Jose A. [3 ]
Carracedo, Arkaitz [1 ,2 ,4 ,5 ]
Sutherland, James D. [1 ]
Barrio, Rosa [1 ]
机构
[1] Basque Res & Technol Alliance, Ctr Cooperat Res Biosci CIC BioGUNE, Bizkaia Technol Pk, Derio, Spain
[2] Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
[3] Univ Basque Country, Univ Pais Vasco, Euskal Herriko Unibertsitatea UPV EHU, Dept Genet Phys Anthropol & Anim Physiol, Leioa, Spain
[4] Ikerbasque, Basque Fdn Sci, Bilbao, Spain
[5] Univ Basque Country UPV EHU, Biochem & Mol Biol Dept, Leioa, Spain
[6] CNRS, ITAV, Pl Pierre Potier Oncopole, Toulouse, France
基金
欧洲研究理事会;
关键词
LUZP1; actin cytoskeleton; proliferation; migration; invasion; cancer; centrosome;
D O I
10.3389/fcell.2021.624089
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:12
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