Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00 Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.
Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00 Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.
Drug Resist Updat. 2020 Sep;52:100691. doi: 10.1016/j.drup.2020.100691. Epub 2020 Mar 4.
Metallothioneins (MTs) are small cysteine-rich intracellular proteins with four major isoforms identified in mammals, designated MT-1 through MT-4. The best known biological functions of MTs are their ability to bind and sequester metal ions as well as their active role in redox homeostasis. Despite these protective roles, numerous studies have demonstrated that changes in MT expression could be associated with the process of carcinogenesis and participation in cell differentiation, proliferation, migration, and angiogenesis. Hence, MTs have the role of double agents, i.e., working with and against cancer. In view of their rich biochemical properties, it is not surprising that MTs participate in the emergence of chemoresistance in tumor cells. Many studies have demonstrated that MT overexpression is involved in the acquisition of resistance to anticancer drugs including cisplatin, anthracyclines, tyrosine kinase inhibitors and mitomycin. The evidence is gradually increasing for a cellular switch in MT functions, showing that they indeed have two faces: protector and saboteur. Initially, MTs display anti-oncogenic and protective roles; however, once the oncogenic process was launched, MTs are utilized by cancer cells for progression, survival, and contribution to chemoresistance. The duality of MTs can serve as a potential prognostic/diagnostic biomarker and can therefore pave the way towards the development of new cancer treatment strategies. Herein, we review and discuss MTs as tumor disease markers and describe their role in chemoresistance to distinct anticancer drugs.
金属硫蛋白（MTs）是富含半胱氨酸的小分子细胞内蛋白，哺乳动物中有 4 种主要的同工型，分别命名为 MT-1 至 MT-4。MTs 最广为人知的生物学功能是其结合和螯合金属离子的能力，以及其在氧化还原平衡中的积极作用。尽管具有这些保护作用，但许多研究表明，MT 表达的变化可能与致癌过程有关，并参与细胞分化、增殖、迁移和血管生成。因此，MT 具有双重作用，即既促进也抑制癌症。鉴于其丰富的生化特性，MT 参与肿瘤细胞化疗耐药的出现并不奇怪。许多研究表明，MT 过表达与包括顺铂、蒽环类药物、酪氨酸激酶抑制剂和丝裂霉素在内的抗癌药物的耐药性获得有关。越来越多的证据表明 MT 功能的细胞转换确实存在两面性：保护者和破坏者。最初，MTs 显示出抗癌和保护作用；然而，一旦致癌过程开始，MTs 就被癌细胞用于进展、存活和促进化疗耐药性。MTs 的双重性可以作为一种潜在的预后/诊断生物标志物，因此为开发新的癌症治疗策略铺平了道路。本文综述并讨论了 MTs 作为肿瘤疾病标志物，并描述了它们在不同抗癌药物化疗耐药性中的作用。
