单羧酸转运体在肿瘤中的功能

Function of the Monocarboxylate Transporter in Tumors

单羧酸转运体(monocarboxylate transporters,MCTs)属于溶质运载蛋白家族(solute carrier family,SLC)SLC16A亚家族成员.目前已发现该家族有14个成员;研究表明,MCTs具有偶联转运细胞新陈代谢中产生的单羧酸与质子的功能.MCTs在肿瘤组织中表达普遍增高,肿瘤细胞是以糖酵解代谢方式获取能量,该过程中产生的大量乳酸被MCTs运出胞外,以保护细胞因酸中毒诱发细胞凋亡;细胞外乳酸也能被肿瘤细胞摄取和利用.由于肿瘤组织的血管不发达,使肿瘤细胞内外的乳酸堆积,导致肿瘤细胞存活在缺氧和酸性微环境中,MCTs对此种环境中肿瘤细胞的存活与转移发挥重要作用.因此,研究肿瘤细胞和正常组织中MCTs的差异性表达及其机制,以及MCTs活性的调控机制,对于认识肿瘤细胞在缺氧和酸性微环境中存活与转移规律具有重要意义,并为肿瘤的治疗提供新的分子靶标.本文将对肿瘤中MCTs的功能研究的最新进展进行综述.同时,结合本室的研究提出一些见解.

Monocarboxylate transporters （MCTs, SLC16A） belong to the subfamily of solute carrier protein family （SLC） consist of 14 members. MCTs are the proton-coupled transporters of monocarboxylates produced in metabolism that widely expressed in tumor tissues. Glycolysis is the most important metabolic pathway for tumor cells to obtain energy, and the produced large amounts of lactate need to be transported out the cells by MCTs, thus to prevent the cells from acidosis-induced apoptosis. The extracellular lactate may also be uptaken and utilized by tumor cells. As tumors are often poorly vascularized, extracellular lactate will lead to hypoxemic and acidic microenvironment, in which MCTs play important roles for tumor cells to survive. To study the different expression and function of MCTs in normal and tumor tissues is important for exploit new targets for the anti-tumor drug development. We reviewed the recent progress about the MCT function in tumors and discussed its implication for future research.