Tempest Robert, Guarnerio Sonia, Maani Rawan, Cooper Jamie, Peake Nicholas
Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK.
Cancers (Basel). 2021 Jun 3;13(11):2788. doi: 10.3390/cancers13112788.
Transglutaminase-2 (TG2) is the most highly and ubiquitously expressed member of the transglutaminase enzyme family and is primarily involved in protein cross-linking. TG2 has been implicated in the development and progression of numerous cancers, with a direct role in multiple cellular processes and pathways linked to apoptosis, chemoresistance, epithelial-mesenchymal transition, and stem cell phenotype. The tumour microenvironment (TME) is critical in the formation, progression, and eventual metastasis of cancer, and increasing evidence points to a role for TG2 in matrix remodelling, modulation of biomechanical properties, cell adhesion, motility, and invasion. There is growing interest in targeting the TME therapeutically in response to advances in the understanding of its critical role in disease progression, and a number of approaches targeting biophysical properties and biomechanical signalling are beginning to show clinical promise. In this review we aim to highlight the wide array of processes in which TG2 influences the TME, focussing on its potential role in the dynamic tissue remodelling and biomechanical events increasingly linked to invasive and aggressive behaviour. Drug development efforts have yielded a range of TG2 inhibitors, and ongoing clinical trials may inform strategies for targeting the biomolecular and biomechanical function of TG2 in the TME.
转谷氨酰胺酶2（TG2）是转谷氨酰胺酶家族中表达最为广泛且含量最高的成员，主要参与蛋白质交联。TG2与多种癌症的发生和发展有关，在与细胞凋亡、化疗耐药性、上皮-间质转化及干细胞表型相关的多个细胞过程和信号通路中发挥直接作用。肿瘤微环境（TME）在癌症的形成、发展及最终转移过程中至关重要，越来越多的证据表明TG2在基质重塑、生物力学特性调节、细胞黏附、迁移及侵袭中发挥作用。随着对TME在疾病进展中的关键作用的认识不断深入，针对TME进行治疗的兴趣日益浓厚，一些针对生物物理特性和生物力学信号的方法已开始展现出临床应用前景。在本综述中，我们旨在强调TG2影响TME的众多过程，重点关注其在与侵袭性和恶性行为日益相关的动态组织重塑和生物力学事件中的潜在作用。药物研发工作已产生了一系列TG2抑制剂，正在进行的临床试验可能为靶向TME中TG2的生物分子和生物力学功能的策略提供依据。
