Bozal-Basterra Laura, Gonzalez-Santamarta María, Muratore Veronica, Martín-Martín Natalia, Ercilla Amaia, Rodríguez Jose A, Carracedo Arkaitz, Sutherland James D, Barrio Rosa
Center for Cooperative Research in Biosciences (CIC BioGUNE), Basque Research and Technology Alliance, Bizkaia Technology Park, Derio, Spain.
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
Front Cell Dev Biol. 2021 Apr 1;9:624089. doi: 10.3389/fcell.2021.624089. eCollection 2021.
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 exhibits frequent genomic aberrations in cancer, with a predominance of gene deletions. Furthermore, we demonstrate that CRISPR/Cas9-mediated loss of 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 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.
LUZP1是一种定位于中心体和肌动蛋白细胞骨架的蛋白质，它调节纤毛发生和肌动蛋白丝束集。由于细胞骨架和纤毛与转移和肿瘤抑制有关，我们研究了LUZP1在癌症背景下的作用。在这里，我们表明LUZP1在癌症中频繁出现基因组畸变，主要是基因缺失。此外，我们证明，在小鼠成纤维细胞中，CRISPR/Cas9介导的LUZP1缺失促进细胞迁移和侵袭特性，降低细胞活力，增加细胞凋亡、中心粒数量和核大小，同时改变肌动蛋白细胞骨架。LUZP1的缺失还诱导了肌动蛋白相关蛋白3（ACTR3，也称为ARP3）和磷酸化丝切蛋白比率的变化，这表明它在肌动蛋白聚合中除了在丝束集中的作用外还具有调节作用。我们的结果表明，LUZP1通过控制肌动蛋白细胞骨架在调节癌症特征方面具有前所未有的作用。
