Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.
Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.
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DOI：
10.18632/oncotarget.26130
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发表时间：
2018-10-02
期刊：
影响因子：
--
通讯作者：
Eckert RL
中科院分区：
文献类型：
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作者：
Adhikary G;Grun D;Alexander HR;Friedberg JS;Xu W;Keillor JW;Kandasamy S;Eckert RL
间皮瘤是一种罕见的胸膜、腹膜、心包和阴道膜间皮细胞层癌症。它通常是由石棉引起的，众所周知，它对化疗具有抵抗力，并且通常被认为无法治愈，预期寿命很短。转谷氨酰胺酶 2 (TG2) 是一种 GTP 结合调节蛋白，是重要的癌症干细胞存活和治疗抵抗因子。我们发现 TG2 在人间皮瘤肿瘤和间皮瘤癌症干细胞（MCS 细胞）中高表达。 TG2 敲低或 TG2 抑制剂治疗可减少 MCS 细胞球体形成、基质胶侵袭、迁移和肿瘤形成。与野生型相比，TG2 敲除细胞的肿瘤首次出现时间延长了一倍。此外，TG2 缺失与干性和上皮间质转化标志物表达减少以及细胞凋亡增强相关。这些研究表明TG2是一种重要的MCS细胞存活蛋白，并表明TG2可以作为间皮瘤癌症干细胞治疗靶点。
Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.