Adhikary Gautam, Grun Daniel, Alexander H Richard, Friedberg Joseph S, Xu Wen, Keillor Jeffrey W, Kandasamy Sivaveera, Eckert Richard L
Departments of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Oncotarget. 2018 Oct 2;9(77):34495-34505. doi: 10.18632/oncotarget.26130.
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.
间皮瘤是一种罕见的癌症，发生于胸膜、腹膜、心包膜和鞘膜的间皮细胞层。它通常由石棉引起，对化疗具有 notoriously 抗性，一般认为无法治愈，预期寿命较短。转谷氨酰胺酶2（TG2）是一种GTP结合调节蛋白，是一种重要的癌症干细胞存活和治疗抗性因子。我们发现TG2在人源间皮瘤肿瘤和间皮瘤癌症干细胞（MCS细胞）中高度表达。TG2基因敲低或TG2抑制剂处理可减少MCS细胞球状体形成、基质胶侵袭、迁移和肿瘤形成。与野生型相比，TG2基因敲除细胞中肿瘤首次出现的时间加倍。此外，TG2缺失与干性和上皮间质转化标志物的表达降低以及细胞凋亡增强有关。这些研究表明TG2是一种重要的MCS细胞存活蛋白，并表明TG2可能作为间皮瘤癌症干细胞治疗靶点。
