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

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.