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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2016; 22(29): 6629-6637
Published online Aug 7, 2016. doi: 10.3748/wjg.v22.i29.6629
Metastasis-associated in colon cancer-1 in gastric cancer: Beyond metastasis
Zhen-Zhen Wu, Li-Shan Chen, Rui Zhou, Jian-Ping Bin, Yu-Lin Liao, Wang-Jun Liao
Zhen-Zhen Wu, Rui Zhou, Wang-Jun Liao, Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Li-Shan Chen, Medical Center for Overseas Patients, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Jian-Ping Bin, Yu-Lin Liao, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: Wu ZZ and Chen LS contributed equally to this work; Wu ZZ, Chen LS and Zhou R performed the research and wrote the paper; Bin JP, Liao YL and Liao WJ critically revised the manuscript for important intellectual content.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wang-Jun Liao, MD, PhD, Department of Oncology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong Province, China. nfyyliaowj@163.com
Telephone: +86-20-62787731 Fax: +86-20-62787731
Received: March 14, 2016
Peer-review started: March 16, 2016
First decision: March 31, 2016
Revised: April 17, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: August 7, 2016
Processing time: 136 Days and 21 Hours
Abstract

Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer (GC), MACC1 has been shown to be involved in oncogenesis and tumor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelial-to-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry (VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.

Keywords: Metastasis-associated in colon cancer-1; Gastric cancer; Epithelial-to-mesenchymal transition; Vasculogenic mimicry; Lymphangiogenesis; Warburg effect; Tumor microenvironment

Core tip: Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is involved in multiple aspects of gastric cancer (GC). Although MACC1 was first identified as a promoter of the epithelial-mesenchymal transition in GC, as in colon cancer, it has subsequently been found to have functions in GC far beyond metastasis, including vasculogenic mimicry, lymphangiogenesis and metabolic reprogramming. These features of tumorigenesis and tumor progression involve both GC cells and the surrounding tumor microenvironment, indicating that the tumor-promoting functions of MACC1 may hinge on its ability to mediate the tumor microenvironment.