各种肿瘤的发生率和病死率不断上升,寻找新型抗肿瘤靶点是抗肿瘤药物开发的主要研究方向之一。经典瞬时受体电位(transient receptor potential canonical, TRPC)通道是位于细胞膜上的一类重要的非选择性阳离子能道,对钠离子(Na+ )、钙离子(Ca2+ )等阳离子具有通透性。该通道家族在体内分布广泛,参与多种生理病理过程。研究表明,多种肿瘤细胞中TRPCs蛋白质水平和mRNA 水平异常高表达,可通过升高肿瘤细胞内Ca2+ 浓度促进肿瘤的增殖。TRPC受体因为定位于细胞膜表面,离子通道靶向药物不需要进入细胞内,使其可能成为理想的治疗靶点,而Ca2+作为细胞内最重要的信使之一,在调节细胞的生长、死亡以及肿瘤细胞增殖和凋亡中起着关键作用。通透Ca2+ 的TRPC通道在肿瘤发生发展中的重要作用,使其成为恶性肿瘤的预后指标和潜在治疗靶点。靶向TRPCs通道调控胞内Ca2+ 浓度,进而调控下游信号通路是抑制肿瘤细胞增殖的新手段。本文综述了TRPC对肿瘤发生发展的影响及机制,并对TRPC家族胞外小分子结合口袋作为抗肿瘤小分子化合物作用靶标的可能性予以关注。
The incidence and mortality of various tumors have been increasing, and the search for novel anti-tumor targets is one of the major research directions for anti-tumor drug development. Transient receptor potential canonical (TRPC) channels are a class of critical non-selective cation channels permeable to sodium (Na+ ), calcium (Ca2+ ), and other cations located on the cell membrane, which are widely distributed in vivo and participate in a variety of physiological and pathological processes. Studies have shown that the protein and mRNA levels of TRPCs are abnormally overexpressed in various tumor cells, which can promote tumor proliferation by increasing the intracellular Ca2+ concentration of tumor cells. Since TRPC receptors are located on the cell surface, ion channel-targeted drugs do not need to enter the cell, making them ideal therapeutic targets. Ca2+ , as one of the most essential intracellular messengers, plays a critical role in regulating cell growth and death, as well as tumor cell proliferation and apoptosis. Ca2+-permeable TRPC channels play a crucial role in tumor development, making them prognostic markers and potential therapeutic targets for malignant tumors. Targeting TRPC channels to regulate intracellular Ca2+ concentration and, in turn, modulate downstream signaling pathways is a novel approach to inhibiting tumor cell proliferation. This review summarizes the effects and mechanisms of TRPCs on tumorigenesis and development, and focuses on the potential of the extracellular small molecule binding pockets of the TRPC family as targets for anti-tumor small molecule compounds.
