瞬时受体电位通道M2在恶性肿瘤中的作用

瞬时受体电位通道M2(transient receptor potential channel melastatin 2, TRPM2)是人体中一个重要的Ca²⁺通透性非选择性阳离子通道,通常表达于正常细胞胞膜和溶酶体膜上,并在氧化应激中发挥重要的离子调节作用。但近年发现,TRPM2也在多种恶性肿瘤(神经母细胞瘤,舌/喉鳞状细胞癌,肺癌,乳腺癌,胃癌,胰腺癌,膀胱癌,前列腺癌和T细胞白血病)中高表达,能通过调节细胞线粒体功能和自噬促进肿瘤细胞的生物学能量而促进其生存能力,通过调节抗氧化物水平增强细胞对氧化刺激的耐受力而表现出化疗抵抗作用。同时,在肿瘤细胞膜上该通道大量激活又对化疗药物联合使用发挥协同作用。此外,TRPM2能通过激活多种不同的分子的信号通路,促进细胞增殖、侵袭和转移能力。总之,根据肿瘤的不同,TRPM2对肿瘤细胞生物学行为的调控机制也不同,甚至具有复杂的双重作用。所以,对TRPM2的生化及分子机制的研究必将使我们对肿瘤的发生发展的认识更加全面。本文将从TRPM2蛋白质的结构,生理功能及肿瘤机制等不同角度系统阐述TRPM2的研究现状和进展。

Role of Transient Receptor Potential Channel Melastatin 2 in Malignant Tumors

Transient receptor potential channel melastatin 2 (TRPM2) which is normally expressed on normal cell membranes and lysosomal membranes, is an important nonselective cation channel for Ca²⁺ permeability and plays a crucial role in oxidative stress in humans. However in recent years, TRPM2 has been found to be highly expressed in various types of malignant tumors (neuroblastoma, tongue/laryngeal squamous cell carcinoma, lung cancer, breast cancer, gastric cancer, pancreatic cancer, bladder cancer, prostate cancer, andT-cell leukemia). It promotes cell viability by regulating mitochondrial function, autophagy, and bioenergetics, and enhances cell resistance to oxidative stimulation by regulating the level of antioxidants. Meanwhile, the massive activation of TRPM2 on the tumor cell membrane, in turn, plays a synergistic effect on the combination of chemotherapeutic drugs. In addition, TRPM2 promotes cell proliferation, invasion, and migration by activating a variety of different molecular signaling pathways. In brief, TRPM2 has different or even dual effects on regulating the biological behaviors of different tumors, and these effects are context-dependent. Therefore, studies of TRPM2 can provide a comprehensive understanding of its roles in oncogenesis and development of tumors. This review summarizes the protein structure, physiological function, and tumor mechanism of TRPM2, and systematically presents the current situation and future progress in this field.