Wang Shuo, Chen Jiang, Guo Xiao-Zhong
Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China.
World J Gastrointest Oncol. 2022 Aug 15;14(8):1388-1405. doi: 10.4251/wjgo.v14.i8.1388.
The gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and prognosis. Cell metabolism dysregulation is an important cause of tumor occurrence, development, and metastasis. As one of the important characteristics of tumors, cell metabolism dysregulation is attracting increasing research attention. Phospholipids are an indispensable substance in the metabolism in various tumor cells. Phospholipid metabolites have become important cell signaling molecules. The pathological role of lysophosphatidic acid (LPA) in tumors was identified in the early 1990s. Currently, LPA inhibitors have entered clinical trials but are not yet used in clinical treatment. Autotaxin (ATX) has lysophospholipase D (lysoPLD) activity and can regulate LPA levels . The LPA receptor family and ATX/lysoPLD are abnormally expressed in various gastrointestinal tumors. According to our recent pre-experimental results, KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating the ATX-LPA axis. However, no relevant research has been reported. Clarifying the mechanism of ATX-LPA in the inhibition of cancer metastasis by KAI1/CD82 will provide an important theoretical basis for targeted cancer therapy. In this paper, the molecular compositions of the gene and the ATX-LPA axis, their physiological functions in tumors, and their roles in gastrointestinal cancers and target therapy are reviewed.
该基因可抑制大多数肿瘤的转移,且与肿瘤侵袭和预后显著相关。细胞代谢失调是肿瘤发生、发展和转移的重要原因。作为肿瘤的重要特征之一,细胞代谢失调正吸引着越来越多的研究关注。磷脂是各种肿瘤细胞代谢中不可或缺的物质。磷脂代谢产物已成为重要的细胞信号分子。溶血磷脂酸(LPA)在肿瘤中的病理作用于20世纪90年代初被发现。目前,LPA抑制剂已进入临床试验阶段,但尚未用于临床治疗。自分泌运动因子(ATX)具有溶血磷脂酶D(lysoPLD)活性,可调节LPA水平。LPA受体家族以及ATX/lysoPLD在各种胃肠道肿瘤中均有异常表达。根据我们最近的实验前结果,KAI1/CD82可能通过调节ATX-LPA轴来抑制癌细胞的迁移和转移。然而,尚未有相关研究报道。阐明ATX-LPA在KAI1/CD82抑制癌症转移中的机制,将为癌症靶向治疗提供重要的理论基础。本文对该基因和ATX-LPA轴的分子组成、它们在肿瘤中的生理功能以及它们在胃肠道癌症和靶向治疗中的作用进行了综述。