Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
School of Sciences, Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, Mommsenstrasse 4, 01307 Dresden, Germany.
Cells. 2022 Apr 14;11(8):1342. doi: 10.3390/cells11081342.
Transglutaminase 2 (TG2) is a protein expressed in many tissues that exerts numerous, sometimes contradictory, intra- and extracellular functions, under both physiological and pathophysiological conditions. In the context of tumor progression, it has been found to be involved in cell adhesion, DNA repair mechanisms, induction of apoptosis, and mesenchymal transdifferentiation, among others. Here, we hypothesized that TG2 also contributes to the radioresistance of two human melanoma cell lines, A375 and MeWo, which can be seen to differ in their basal TG2 biosynthesis by examining their proliferation and clonal expansion after irradiation. For this purpose, cellular TG2 biosynthesis and TG2 activity were modulated by transfection-induced overexpression or TG2 knock-out and application of TG2-selective inhibitors. Proliferation and clonal expansion of TG2-overexpressing cells was not enhanced over wildtype cells, suggesting that increased TG2 biosynthesis does not further enhance the radioresistance of melanoma cells. Conversely, TG2 knock-out in A375 cells reduced their proliferation, as well as clonal and spheroidal expansion after irradiation, which indicates a contribution of TG2 to the radioresistance of melanoma cells. Since TG1, TG3, and partly also, TG6 biosynthesis was detectable in A375 and MeWo cells, it can be assumed that these other members of the TG family may exert a partially compensatory effect.
转谷氨酰胺酶 2（TG2）是一种在许多组织中表达的蛋白质，在生理和病理生理条件下，它具有许多、有时是相互矛盾的细胞内和细胞外功能。在肿瘤进展的背景下，已经发现它参与细胞黏附、DNA 修复机制、细胞凋亡诱导和间充质转化等过程。在这里，我们假设 TG2 也有助于两种人黑色素瘤细胞系 A375 和 MeWo 的放射抵抗性，通过观察照射后细胞增殖和克隆扩增，可以发现它们的基础 TG2 生物合成存在差异。为此，通过转染诱导过表达或 TG2 敲除以及应用 TG2 选择性抑制剂来调节细胞 TG2 生物合成和 TG2 活性。与野生型细胞相比，过表达 TG2 的细胞的增殖和克隆扩增并没有增强，这表明增加 TG2 生物合成并不能进一步增强黑色素瘤细胞的放射抵抗性。相反，A375 细胞中 TG2 的敲除减少了其增殖以及照射后的克隆和球体扩张，这表明 TG2 有助于黑色素瘤细胞的放射抵抗性。由于在 A375 和 MeWo 细胞中可检测到 TG1、TG3 和部分 TG6 的生物合成，因此可以假设 TG 家族的这些其他成员可能发挥部分补偿作用。
