MCT4 - a key player influencing gastric cancer metastasis and participating in the regulation of the metastatic immune microenvironment - research open access

Sep 23, 2026

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MCT4 is a lactate transporter linked to glycolysis and has been implicated in multiple steps of tumorigenesis, yet its specific role in gastric cancer remains unclear. This study integrates single-cell sequencing with external transcriptome databases to define how MCT4 influences gastric cancer and its microenvironment. Functional validation uses in vitro cell assays and in vivo gastric cancer liver metastasis and subcutaneous tumor models, supported by immunohistochemistry and multiplex immunofluorescence on clinical samples.

LanguageEnglish

CategoryHealthcare

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Pages16

Reading Time40 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

Jiang et al. Journal of Translational Medicine (2025) 23:276 [https://doi.org/10.1186/s12967-025-06279-8](https://doi.org/10.1186/s12967-025-06279-8) Journal of Translational Medicine RESEARCH Open Access MCT4: a key player influencing gastric cancer metastasis and participating in the regulation of the metastatic immune microenvironment Tao Jiang1,2, Jingcheng Zhang1,2, Sicheng Zhao1,2, Mingsi Zhang3, Yunhai Wei4, Xiaojuan Liu1,2, Shuo Zhang1,2, Wei Fan1,2, Yueying Liu1,2, Yuanlin Lv1* and Guangji Zhang1,2* Abstract Background MCT4 is a lactate transporter associated with glycolysis, which has been found to be associated with various tumorigenesis and development processes. Gastric cancer is a malignant disease with high incidence and mortality. The role of MCT4 in the occurrence and development of gastric cancer has not been clarified. Methods In this study, we comprehensively utilized single-cell sequencing and external transcriptome sequencing databases to deeply analyze the mechanism of the impact of MCT4 on gastric cancer and its microenvironment. We verified the function of MCT4 in gastric cancer through in vitro cell line experiments and in vivo experiments using gastric cancer liver metastasis and subcutaneous tumor models. Meanwhile, we collected tumor and normal tissue samples from clinical gastric cancer patients and employed immunohistochemistry and multiplex immunofluorescence techniques to detect the expression and localization of relevant indicators, thereby validating the results of computer simulation analysis and providing a basis for revealing the internal relationship between MCT4 and gastric cancer. Results The expression of MCT4 is upregulated in gastric cancer patients, and the upregulation is more significant than that in patients with gastric cancer metastasis. MCT4 can mediate the proliferation and migration of gastric cancer cells in vitro. MCT4 can mediate the metastasis of gastric cancer cells in vivo. Multi-omics analysis showed that the expression of MCT4 was related to the composition of the immune microenvironment, and it could mediate the emergence of the inhibitory immune microenvironment. The results of immunofluorescence and immunohistochemistry proved the robustness of the multi-omics analysis. Conclusion Our study found that MCT4 plays an important role in the occurrence and development of gastric cancer, which may mediate the occurrence of gastric cancer metastasis and shape the immunosuppressive tumor microenvironment. Keywords SLCA16A3, MCT4, Gastric cancer metastasis, Immune microenvironment, EMT *Correspondence: Yuanlin Lv [lvyuanlin99@163.com](lvyuanlin99@163.com)[ ](lvyuanlin99@163.com)Guangji Zhang [zgjtcm@zcmu.edu.cn](zgjtcm@zcmu.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Jiang et a

FAQs

What did the results show about MCT4 and the tumor immune microenvironment?

MCT4 expression was upregulated in gastric cancer, especially in metastatic cases. Multi-omics analysis and immunohistochemistry/immunofluorescence supported that MCT4 relates to immune microenvironment composition and may contribute to an inhibitory immune microenvironment.

Sep 23, 2026

Uploaded by Theodore