Xie Jing, Zhu Xiao Yan, Liu Lu Ming, Meng Zhi Qiang
Department of Integrative Oncology, Fudan University Shanghai Cancer Center.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
Cancer Manag Res. 2018 Jan 24;10:153-166. doi: 10.2147/CMAR.S152951. eCollection 2018.
Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.
消化系统肿瘤是全球癌症相关死亡的主要原因。溶质载体(SLC)超家族由一系列转运蛋白组成,这些转运蛋白在消化系统的器官和组织中广泛表达,并以易化方式介导小分子底物的特异性摄取。鉴于SLC蛋白在维持消化系统正常功能中的重要作用,这些蛋白在消化系统肿瘤中的失调可能具有生物学和临床意义,值得进行系统研究。在本综述中,我们批判性地总结了在理解SLC蛋白在消化系统肿瘤中的作用方面的最新进展。我们强调,几个SLC亚家族,包括金属离子转运蛋白、葡萄糖和其他糖类转运蛋白、尿素转运蛋白、神经递质和生物胺转运蛋白、铵和胆碱转运蛋白、无机阳离子/阴离子转运蛋白、核苷酸转运蛋白、氨基酸和寡肽有机阴离子转运蛋白、维生素和辅因子转运蛋白以及线粒体载体,可能在介导消化系统肿瘤的发生、发展、转移和化疗耐药中发挥重要作用。这些SLC亚家族中的蛋白对特定癌症类型也可能具有诊断和预后价值。通过从人类癌症数据库中提取数据,分析了消化系统肿瘤中SLC蛋白的差异表达,结果显示SLC蛋白的作用可能既取决于它们转运的底物,也具有组织特异性。此外,还讨论了通过药理学调节SLC蛋白功能的小分子调节剂在消化系统肿瘤治疗中的可能应用。本综述强调了SLC家族蛋白作为消化系统肿瘤治疗药物靶点的潜力。