ATIC facilitates the malignant progression of bladder cancer by modulating AMPK-mTOR-S6K1 axis under folate reprogramming

Sep 22, 2026

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Metabolic reprogramming underpins cancer, while the impact of ATIC-mediated folate metabolism in bladder and other solid tumors remains insufficiently characterized. This study links ATIC to folate metabolic reprogramming, positioning folate metabolism as an actionable vulnerability for broadly applicable oncology therapies. Using multi-dataset and clinical evidence, ATIC is assessed across expression, prognosis, metabolic features, microenvironment, drug resistance, and pathway networks.

LanguageEnglish

CategoryResearch & Report

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Pages18

Reading Time45 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Xu etal. Journal of Translational Medicine (2026) 24:429 [https://doi.org/10.1186/s12967-026-07830-x](https://doi.org/10.1186/s12967-026-07830-x) Journal of Translational Medicine RESEARCH Open Access ATIC facilitates the malignant progression of bladder cancer by modulating AMPK mTOR-S6K1 axis under folate reprogramming Da-Ming Xu1,2†, Jie Chen3†, Shu-Bin Lin3†, Teng-Yu Xu3, Ze-Zhou Zhan3, Zheng-Liang Yang3, You-Bin Peng3, Hao Lin3, Jun Yin4,5*, Ming Li3* and Xin-Cheng Liu3* Abstract Background Metabolic reprogramming is a hallmark of cancer, yet the role of ATIC-mediated folate metabolism in bladder and other solid tumors remains understudied. Due to its critical role in cancer cell growth, folate metabolism could be a promising target for novel, broadly applicable cancer therapies. Methods This study integrated multiple bladder cancer datasets from TCGA, GEO, and clinical data from 80 patients at our hospital to explore the relationship between ATIC and folate metabolism. We focused on expression patterns, prognosis, metabolic processes, microenvironment, drug resistance, and associated pathways. Through multi-omics analysis, 97 single-cell datasets, 18 spatial tissue slices, and machine learning approaches, we assessed ATIC as a pancancer driver and identified key folate metabolism-related driver genes. Results We found that ATIC overexpression in bladder cancer was linked to poor prognosis, GC chemotherapy resistance, elevated cancer folate levels, and malignant phenotypes. Our study first proposed that ATIC promotes bladder cancer progression by regulating the AMPK-mTOR-S6K1 axis under folate reprogramming. We also validated ATIC-folate reprogramming crosstalk across cancers through pan-cancer analysis and created a multi-cancer folate metabolism-driven gene map, highlighting the importance of ATIC and folate metabolism in future oncology research. Conclusions Our study identifies ATIC as a key cancer driver gene. Targeting ATIC offers a promising therapeutic strategy, especially for bladder cancer and potentially other cancers with disrupted folate metabolism. These findings highlight new treatment possibilities targeting metabolic vulnerabilities in cancer. Keywords ATIC, Folate metabolism, Bladder cancer, Large-scale single-cell transcriptomics, Spatial transcriptomics †Da-Ming Xu, Jie Chen and Shu-Bin Lin contributed to the work equally and should be regarded as co-first authors. *Correspondence: Jun Yin [jyin@stu.edu.cn](jyin@stu.edu.cn)[ ](jyin@stu.edu.cn)Ming Li[lmdoctor@21cn.com](lmdoctor@21cn.com)[ ](lmdoctor@21cn.com)Xin-Cheng Liu [liuxincheng321@163.com](liuxincheng321@163.com) 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China 2Department of Urology, SunYat-Sen University Cancer Center, Guangzhou 510060, P. R. China 3Department of Urology, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, P. R. China 4Department of Clinical Laboratory Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, P. R. China 5Division of Hematology, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, P. R. China © The Author(s) 2026. 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 indica

FAQs

What is the central question of the study?

The study investigates how ATIC-mediated folate metabolism influences bladder cancer progression and related malignancy traits, including links to metabolic pathways.

How was ATIC and folate metabolism relationship analyzed?

Multiple bladder cancer datasets from TCGA, GEO, and clinical data from 80 patients were integrated, with focus on expression patterns, prognosis, metabolic processes, microenvironment, drug resistance, and associated pathways.

What mechanism does the paper propose for ATIC-driven bladder cancer progression?

The paper proposes that ATIC promotes progression by regulating the AMPK-mTOR-S6K1 axis under folate reprogramming, supported by multi-omics and pan-cancer validation.

Sep 22, 2026

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