Research Paper|Volume 13, Issue 4|pp 5197—5225

High expression of vinculin predicts poor prognosis and distant metastasis and associates with influencing tumor-associated NK cell infiltration and epithelial-mesenchymal transition in gastric cancer

Huafu Li^1,^2,³, Chunming Wang^1,², Linxiang Lan³, Axel Behrens³, Mona Tomaschko³, Josue Ruiz³, Qiao Su⁴, Guangying Zhao³, Cheng Yuan⁵, Xing Xiao^1,⁶, Bo Li^1,⁶, Leping Yan⁶, Wang Wu^1,², Wuguo Li⁴, Junzong Chen¹, Yulong He^1,², Changhua Zhang^1,²

¹Digestive Medicine Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
²Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
³Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK
⁴Animal Experiment Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
⁵Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Centre Singapore, Singapore
⁶Center of Scientific Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China

* Co-first author

Received: June 3, 2020Accepted: October 27, 2020Published: February 1, 2021

https://doi.org/10.18632/aging.202440

Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

In the process of epithelial-mesenchymal transition (EMT), epithelial cancer cells transdifferentiate into mesenchymal-like cells with high motility and aggressiveness, resulting in the spread of tumor cells. Immune cells and inflammation in the tumor microenvironment are the driving factors of EMT, but few studies have explored the core targets of the interaction between EMT and tumor immune cells. We analyzed thousands of cases of gastric cancer and gastric tissue specimens of TCGA, CPTAC, GTEx and analyzing QPCR and IHC data of 56 gastric cancer patients in SYSU Gastric Cancer Research Center. It was known that EMT has an important connection with the infiltration of NK cells, and that the expression of vinculin may be the target of the phenomenon. The increased expression of vinculin is closely related to the aggressiveness and distant metastasis of cancer, which affects the survival prognosis of the patient. Moreover, through in vitro experiments under 3D conditions, we found that vinculin, cell invasion and metastasis are clearly linked. VCL can affect EMT and tumor immunity by regulating EPCAM gene expression. The role and mechanism of action of vinculin have been controversial, but this molecule may downregulate EpCAM (epithelial cellular adhesion molecule) and its own role in gastric cancer through DNA methylation, causing NK cells to enrich into tumor cells and kill tumor cells. At the same time, it promotes the occurrence of EMT, which in turn causes tumor metastasis and thus poorer prognosis.