Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University Hefei, China ; Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University Guangzhou, China ; Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University Guangzhou, China ; Research Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty of Mannheim, Heidelberg University Mannheim, Germany.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University Hefei, China.
Am J Cancer Res. 2015 Aug 15;5(9):2756-76. eCollection 2015.
The significant influence of tumor microenvironment on malignant cells has been investigated with enthusiasm in this era of targeted therapy. Transglutaminase 2 (TG2, EC 2.3.2.13), a multi-functional enzyme that catalyzes the formation of intermolecular isopeptide bonds between glutamine and lysine side-chains, has been reported to exert important pathophysiological functions. The aim of this review was to investigate the correlation between TG2 and malignant behaviors, which could provide the rationale for novel approaches in anti-cancer therapy. We performed a systematic and electronic search on Medline, Scopus, and Web of Science for relevant publications from inception to April 2015. The bibliographic references of retrieved articles were further reviewed for additional relevant studies. TG2 exerts important physiological functions and plays vital roles in inflammation mainly through its modulation on the structure and stability of extracellular matrix (ECM). It also regulates EMT of diverse malignant cells through various intracellular and extracellular pathways. TG2 also plays an important role in tumor progression and may serve as a novel prognostic biomarker and therapeutic target in various cancer types. TG2 promotes malignant cell mobility, invasion, and metastasis, and induces chemo-resistance of cancer cells, mainly through its pro-crosslink and signaling transduction mediation propensities. In conclusion, TG2 plays vital roles in malignancy progression, and may have important prognostic and therapeutic significances.
在靶向治疗时代，人们对肿瘤微环境对恶性细胞的显著影响进行了热烈的研究。转谷氨酰胺酶 2（TG2，EC 2.3.2.13）是一种多功能酶，能够催化谷氨酰胺和赖氨酸侧链之间形成分子间异肽键，据报道具有重要的病理生理功能。本综述旨在探讨 TG2 与恶性行为之间的相关性，为癌症治疗的新方法提供理论依据。我们对 Medline、Scopus 和 Web of Science 进行了系统的电子检索，以获取从创建到 2015 年 4 月的相关出版物。还进一步查阅了检索文章的参考文献，以获取其他相关研究。TG2 发挥着重要的生理功能，主要通过调节细胞外基质（ECM）的结构和稳定性在炎症中发挥重要作用。它还通过各种细胞内和细胞外途径调节多种恶性细胞的 EMT。TG2 在肿瘤进展中也起着重要作用，并可能成为各种癌症类型的新型预后生物标志物和治疗靶点。TG2 促进恶性细胞的迁移、侵袭和转移，并诱导癌细胞的化疗耐药性，主要通过其促进交联和信号转导的倾向。总之，TG2 在肿瘤的恶性进展中起着至关重要的作用，可能具有重要的预后和治疗意义。
