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World J Gastrointest Oncol. Aug 15, 2022; 14(8): 1388-1405
Published online Aug 15, 2022. doi: 10.4251/wjgo.v14.i8.1388
KAI1/CD82 gene and autotaxin-lysophosphatidic acid axis in gastrointestinal cancers
Shuo Wang, Jiang Chen, Xiao-Zhong Guo
Shuo Wang, Jiang Chen, Xiao-Zhong Guo, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
Author contributions: Wang S wrote the original draft; Chen J and Guo XZ contributed to the review and manuscript editing.
Supported by the National Natural Science Foundation of China, No. 81672465; and the Science and Technology Program of Liaoning Province, No. 2019JH8/10300080.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Zhong Guo, PhD, Chief Doctor, Chief Physician, Director, Professor, Department of Gastroenterology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110840, Liaoning Province, China. guoxiaozhong1962@126.com
Received: November 11, 2021
Peer-review started: November 11, 2021
First decision: December 27, 2021
Revised: January 6, 2022
Accepted: July 22, 2022
Article in press: July 22, 2022
Published online: August 15, 2022
Abstract

The KAI1/CD82 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 in vivo. 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 KAI1/CD82 gene and the ATX-LPA axis, their physiological functions in tumors, and their roles in gastrointestinal cancers and target therapy are reviewed.

Keywords: KAI1/CD82, Autotaxin, Lysophosphatidic acid, Pancreatic cancer, Liver cancer

Core Tip: The KAI1/CD82 gene inhibits the metastasis of most tumors and is significantly correlated with their invasion and prognosis. According to our recent pre-experimental results, we speculated that KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating autotaxin (ATX)-lysophosphatidic acid (LPA) axis. However, no relevant research has been reported. To clarify the mechanism of ATX-LPA in KAI1/CD82 inhibition of cancer metastasis will provide an important theoretical basis for targeted cancer therapy, and further research is necessary. In this paper, the molecular composition of the KAI1/CD82 gene and ATX-LPA axis, their physiological functions in tumors, and their roles in gastrointestinal cancers and target therapy are reviewed.