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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 the first cell-related molecule identified by our institute. In vitro and in vivo studies have shown that the high expression of TMEM106A in gastric cancer cells can significantly inhibit tumor cell growth and induce cell death. In this study, using tissue microarray and immunohistochemistry, we found that TMEM106A protein is highly expressed in non-cancerous non-cancerous tissues, mainly located in the cytoplasm, but not expressed in hepatoma cells. Further functional studies demonstrated that high expression of TMEM106A in Hep G2 cells decreased cell viability, induced cytoplasmic vacuolization and cell cycle arrest at G2 / M phase, resulting in cell death. Cytoplasmic aggregates of vacuoles appear as monolayer membranes, which are essentially free of subcellular organelle structures and high electron density aggregates. This study shows for the first time that TMEM106A can cause the death of macrophage-like cells and its mechanism of action needs to be further explored.