跨膜蛋白TMEM106A诱导肝癌细胞HepG2巨泡样死亡

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HepG2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) TMEM106A Induces Methuosis of HepG2 Liver Cancer Cells

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 TMEM106A 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 TMEM106A expression is lost or reduced in liver cancer samples. However, the expression of TMEM106A 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 TMEM106A overexpression in HepG2 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 or high density aggregates. This is the first study which shows that TMEM106A can cause methuosis. The molecular mechanism of TMEM106A needs to be further explored.