GALNT6 promotes bladder cancer malignancy and immune escape by epithelial-mesenchymal transition and CD8 + T cells

Sep 21, 2026

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Bladder cancer (BC) ranks among the most common male cancers globally and has limited effectiveness of conventional surgery, radiation, chemotherapy, and immunotherapy in advanced cases. This study clarifies the clinical and mechanistic role of GALNT6-mediated abnormal O-glycosylation in BC. GALNT6 is significantly upregulated in tumors, where high expression associates with advanced stage, higher grade, poor overall survival, and worse prognosis. It promotes tumor growth, migration, and invasion via EMT pathway activation and shows an inverse relationship with CD8+ T cell infiltration in the tumor microenvironment, supporting GALNT6 as a driver of immune escape.

LanguageEnglish

CategoryResearch & Report

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Pages18

Reading Time45 min

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Sun et al. Cancer Cell International (2024) 24:308 Cancer Cell International [https://doi.org/10.1186/s12935-024-03492-1](https://doi.org/10.1186/s12935-024-03492-1) RESEARCH Open Access GALNT6 promotes bladder cancer malignancy and immune escape by epithelialmesenchymal transition and CD8 + T cells Xiaoxin Sun 1,2†, Haotian Wu 1†, Ling Tang 1†, Abdullah Al-Danakh3, Yuli Jian 1, Li Gong 1, Congchen Li 1, Xiao Yu4, Guang Zeng2, Qiwei Chen3,5*, Deyong Yang3* and Shujing Wang 1* Abstract Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8+ T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC. Keywords GALNT6, O-glycosylation, Epithelial-mesenchymal transition, Tumor immune escape, Bladder cancer †Xiaoxin Sun, Haotian Wu and Ling Tang contributed equally to this work. *Correspondence: Qiwei Chen[chenqiwei@dmu.edu.cn](chenqiwei@dmu.edu.cn)[ ](chenqiwei@dmu.edu.cn)Deyong Yang [yangdeyong@dmu.edu.cn](yangdeyong@dmu.edu.cn)[ ](yangdeyong@dmu.edu.cn)Shujing Wang [wangshujing@dmu.edu.cn](wangshujing@dmu.edu.cn) 1Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China 2College of Integrative Medicine, Dalian Medical University, Dalian 116044, China 3Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian 116000, China 4Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China 5Zhongda Hospital, Medical School, Advanced Institute for Life and Health, Southeast University, 210096 Nanjing, China © The Author(s) 2024. 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

FAQs

What is the main focus of this research on bladder cancer?

The research investigates how GALNT6-mediated abnormal O-glycosylation contributes to bladder cancer malignancy and immune evasion through EMT and CD8+ T cell dynamics.

How does GALNT6 expression relate to clinical outcomes in bladder cancer?

High GALNT6 expression correlates with advanced stage and high grade, leading to poor overall survival and an unfavorable prognosis.

What experimental evidence links GALNT6 to tumor behavior and immune escape?

In vitro and in vivo experiments show that elevated GALNT6 levels are associated with increased tumor growth, migration, and invasion, while higher GALNT6 levels are inversely related to CD8+ T cell infiltration in the tumor microenvironment.

Sep 21, 2026

Uploaded by Theodore