跨膜蛋白TMEM106A诱导肝癌细胞HepG2巨泡样死亡  

Transmembrane Protein 106A( TMEM106A) Induces Methuosis of HepG2 Liver Cancer Cells

作　　者：许冬[1,2] 姜静远 许晨彤 林欣[2,3] 夏艳[2,3] 王晓琨[3] 潘欢[3] 陈英玉[2,3] 

机构地区：[1]北京大学第一医院检验科,北京100034 [2]北京大学基础医学院免疫学系,北京100191 [3]北京大学人类疾病基因研究中心,北京100191

出　　处：《中国生物化学与分子生物学报》2017年第1期44-50,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家重点基础研究发展计划(973;No.2011CB910103);国家自然科学基金国家基础科学人才培养基金(No.J1030831/J0108);北京大学第一医院科研基金(No.2016QN13)资助~~

摘　　要：跨膜蛋白106A(transmembrane protein 106A,TMEM106A)是本中心首先鉴定的与细胞死亡相关的分子。体内外的功能研究证明,TMEM106A在胃癌细胞的高表达能够明显抑制肿瘤细胞的生长,并诱导细胞死亡。本研究利用组织芯片和免疫组化的方法,发现TMEM106A蛋白在癌旁非肿瘤组织中高表达,主要定位在胞质,而在肝癌细胞中低表达或者不表达。进一步的功能研究证明TMEM106A在肝癌细胞系Hep G2中高表达能够降低细胞活力、诱导胞质空泡化以及细胞周期阻滞在G2/M期,最终细胞死亡。胞质聚集的空泡表现为单层膜,液泡内基本不含亚细胞器结构以及高电子密度的聚集物。本研究首次证明TMEM106A能够引起巨泡样细胞死亡,其作用机制需要进一步探讨。Transmembrane protein 106A（ TMEM106A） is a novel human cell death-related molecule identified in our laboratory for the first time. Functional studies demonstrated that overexpression of TMEM106 A in gastric cancer cells significantly inhibits the growth of tumor cells and induces cell death.In the present report,using tissue microarray and immunohistochemistry,we observed that TMEM106 A expression is lost or reduced in liver cancer samples. However,the expression of TMEM106 A protein was strong positive in most non-tumor tissues adjacent to cancer,which was mainly localized in the cytoplasm of the cell. Further study proved that TMEM106 A overexpression in Hep G2 cells could decrease cell viability,induce cytoplasmic vacuolization and growth arrest at G2/ M phase,and finally cell death.These cytoplasmic vacuoles showed a single membrane,in which contained no subcellular organelles orhigh density aggregates. This is the first study which shows that TMEM106 A can cause methuosis. The molecular mechanism of TMEM106 A needs to be further explored.

关 键 词：跨膜蛋白106A 胞质空泡化 巨泡样死亡 细胞死亡 肝癌 

分 类 号：Q25[生物学—细胞生物学] Q731