Wang Manna, Ning Xiangkai, Chen Ang, Huang Hongyan, Ni Chao, Zhou Changxi, Yu Kaitao, Lan Sanchun, Wang Qiwei, Li Shichong, Liu Hong, Wang Xiaoning, Chen Zhaolie, Ma Li, Sun Qiang
1] Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou 510515, P. R. China [2] Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, P. R. China.
Laboratory of Cell Engineering, Institute of Biotechnology, 20 Dongda Street, Beijing 100071, P. R. China.
Sci Rep. 2015 Jul 20;5:12223. doi: 10.1038/srep12223.
Although cell-in-cell structures (CICs) could be detected in a wide range of human tumors, homotypic CICs formed between tumor cells occur at low rate for most of them. We recently reported that tumor cells lacking expression of E- and P-cadherin were incapable of forming homotypic CICs by entosis, and re-expression of E- or P-cadherin was sufficient to induce CICs formation in these tumor cells. In this work, we found that homotypic CICs formation was impaired in some tumor cells expressing high level of E-cadherin due to loss expression of alpha-catenin (α-catenin), a molecular linker between cadherin-mediated adherens junctions and F-actin. Expression of α-catenin in these tumor cells restored cell-cell adhesion and promoted CICs formation in a ROCK kinase-dependent way. Thus, our work identified α-catenin as another molecule in addition to E- and P-cadherin that were targeted to inactivate homotypic CICs formation in human tumor cells.
尽管在多种人类肿瘤中都能检测到细胞内细胞结构（CICs），但对大多数肿瘤而言，肿瘤细胞之间形成的同型CICs发生率较低。我们最近报道，缺乏E-钙黏蛋白和P-钙黏蛋白表达的肿瘤细胞无法通过内吞作用形成同型CICs，而重新表达E-钙黏蛋白或P-钙黏蛋白足以诱导这些肿瘤细胞形成CICs。在这项研究中，我们发现由于α-连环蛋白（α-catenin）表达缺失，一些高表达E-钙黏蛋白的肿瘤细胞中同型CICs形成受损，α-连环蛋白是钙黏蛋白介导的黏附连接与F-肌动蛋白之间的分子连接物。在这些肿瘤细胞中表达α-连环蛋白可恢复细胞间黏附，并以ROCK激酶依赖性方式促进CICs形成。因此，我们的研究确定α-连环蛋白是除E-钙黏蛋白和P-钙黏蛋白之外的另一种分子，其靶向作用是使人类肿瘤细胞中的同型CICs形成失活。
