FAM21C Promotes Hepatocellular Carcinoma Invasion and Metastasis by Driving Actin Cytoskeleton Remodeling via Inhibiting Capping Ability of CAPZA1.
FAM21C Promotes Hepatocellular Carcinoma Invasion and Metastasis by Driving Actin Cytoskeleton Remodeling via Inhibiting Capping Ability of CAPZA1.
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DOI：
10.3389/fonc.2021.809195
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Lu Y;Huang D;Wang B;Zheng B;Liu J;Song J;Zheng S
肝细胞癌（HCC）的特点是高转移率。肌动蛋白细胞骨架的动态重构在肝癌细胞的侵袭和迁移中起着重要作用。在前期的研究中，我们发现CAPZA 1作为一种加帽蛋白，可以通过调节肌动蛋白微丝（F-actin）细胞骨架的重塑来促进肝癌细胞的EMT，从而促进肝癌细胞的侵袭和迁移。本研究发现FAM 21 C可能对CAPZA 1具有调控作用，并对其潜在的调控机制进行了深入研究。首先，我们发现FAM 21 C在HCC组织中高表达，并且其高表达可促进HCC的恶性进展。FAM 21 C的高表达促进了肝癌细胞在体外和体内的侵袭和迁移。此外，FAM 21 C与CAPZA 1相互作用，它们的结合抑制CAPZA 1的加帽能力，从而促进HCC细胞的侵袭和迁移。FAM 21 C的这种作用通过突变CP相互作用（CPI）结构域（FAM 21 C上的CAPZA 1结合位点）而消除。结论：FAM 21 C在肝癌组织中的高表达可促进肝癌的恶性进展，其机制可能与FAM 21 C通过与CAPZA 1结合抑制CAPZA 1的加帽能力，从而驱动F-actin细胞骨架重塑，从而促进肝癌细胞的侵袭和迁移有关。
Hepatocellular carcinoma (HCC) is characterized by a high incidence of metastasis. The dynamic remodeling of the actin cytoskeleton plays an important role in the invasion and migration of HCC cells. In previous studies, we found that CAPZA1, a capping protein, can promote EMT of HCC cells by regulating the remodeling of the actin filament (F-actin) cytoskeleton, thus promoting the invasion and migration of HCC cells. In this study, we found that FAM21C may have a regulatory effect on CAPZA1, and we conducted an in-depth study on its potential regulatory mechanism. First, we found that FAM21C is highly expressed in HCC tissues and its high expression could promote the malignant progression of HCC. Meanwhile, the high expression of FAM21C promoted the invasion and migration of HCC cells in vitro and in vivo. Further, FAM21C interacted with CAPZA1, and their binding inhibited the capping capacity of CAPZA1, thus promoting the invasion and migration of HCC cells. This effect of FAM21C was abolished by mutating the CP-interacting (CPI) domain, the CAPZA1 binding site on FAM21C. In conclusion, high expression of FAM21C in HCC tissues can promote malignant progression of HCC and its potential mechanism involves FAM21C inhibition of CAPZA1 capping capacity by binding to CAPZA1, which drives F-actin cytoskeleton remodeling, and thus promotes invasion and migration of HCC cells.
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影响因子：
7.2
作者：
Gautreau, Alexis;Oguievetskaia, Ksenia;Ungermann, Christian
通讯作者：
Ungermann, Christian
缺氧通过 PIP2 调节 CAPZA1 与 F-肌动蛋白的结合诱导肌动蛋白细胞骨架重塑，驱动肝细胞癌中的 EMT
影响因子：
9.7
作者：
Huang, Deng;Cao, Li;Zheng, Shu-guo
通讯作者：
Zheng, Shu-guo
影响因子：
64.8
作者：
Huttlin EL;Bruckner RJ;Paulo JA;Cannon JR;Ting L;Baltier K;Colby G;Gebreab F;Gygi MP;Parzen H;Szpyt J;Tam S;Zarraga G;Pontano-Vaites L;Swarup S;White AE;Schweppe DK;Rad R;Erickson BK;Obar RA;Guruharsha KG;Li K;Artavanis-Tsakonas S;Gygi SP;Harper JW
通讯作者：
Harper JW
DOI：
10.1083/jcb.201306162
发表时间：
2013-12-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Monteiro P;Rossé C;Castro-Castro A;Irondelle M;Lagoutte E;Paul-Gilloteaux P;Desnos C;Formstecher E;Darchen F;Perrais D;Gautreau A;Hertzog M;Chavrier P
通讯作者：
Chavrier P
CAPZA1 通过调节肝细胞癌肌动蛋白细胞骨架重塑来调节 EMT
DOI：
10.1186/s13046-016-0474-0
发表时间：
2017-01-16
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Huang D;Cao L;Zheng S
通讯作者：
Zheng S