文献类型：期刊文献

英文题名：Mechanical stress, metabolic reprogramming and stromal remodeling: an emerging paradigm in the bladder cancer mechano-micro-environment

作者：Dong, Xiaofei[1,2];Chen, Zixuan[2];Chen, Yi[2];Xiao, Zheng[2];Zhang, Jingjing[2];Li, Yingcun[2,3];Du, Haifang[1]

第一作者：Dong, Xiaofei

通信作者：Du, HF[1];Li, YC[2];Li, YC[3]

机构：[1]Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China;[2]Gansu Univ Chinese Med, Dept Basic Med Sci, Lanzhou, Peoples R China;[3]Dunhuang Med Literature Compilat & Applicat Res Ct, Gansu Prov Key Res Base Humanities & Social Sci, Lanzhou, Peoples R China

第一机构：Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China

通信机构：[1]corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Dept Basic Med Sci, Lanzhou, Peoples R China;[3]corresponding author), Dunhuang Med Literature Compilat & Applicat Res Ct, Gansu Prov Key Res Base Humanities & Social Sci, Lanzhou, Peoples R China.|[107351d2d02a88e1f325f]甘肃中医药大学基础医学院（敦煌医学研究所）;[10735]甘肃中医药大学;

年份：2026

卷号：17

外文期刊名：FRONTIERS IN GENETICS

收录：;Scopus(收录号：2-s2.0-105046925803);WOS:【SCI-EXPANDED(收录号:WOS:001840517700001)】；

基金：The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the National Natural Science Foundation of China (No. 82174285); National Natural Science Foundation of China (82304703); Dunhuang Medical Literature Collation and Application Research Center Project, Key Research Base of Humanities and Social Sciences in Universities of Gansu Province (No. DHYXJD 2025); National Social Science Fund of China (No. 22BYY038); Education Department of Gansu Province: "Innovation Star" Project for Excellent Graduate Students (No. 2026CXCY-006).

语种：英文

外文关键词：Bladder cancer; mechanical stress; mechanotransduction; metabolic reprogramming; stromal remodeling

摘要：Recently managing bladder cancer (BLCA) has been hampered by two stubborn challenges, one is high recurrence rate in non-muscle-invasive tumors (NMIBC), the other is muscle-invasive disease (MIBC) showed limited responsiveness to immune checkpoint inhibitors (ICIs). Tumor micro-environment (TME) is characterized exclusively, while the physical and mechanical forces that actively remodel tumors have been largely overlooked. The bladder, a mechanically dynamic organ that undergoes continuous cycles of filling and voiding, provides an exceptionally instructive model for dissecting tumor biology driven by mechanical stress. In this review, we systematically delineates how mechanical stresses in BLCA, including extracellular matrix (ECM) stiffening, solid stress, fluid shear stress, and cyclic stretch-drive metabolic reprogramming, resulting in enhanced glycolysis, glutamine metabolic remodeling, and lactate accumulation. These metabolic alterations subsequently promote fibroblast activation, collagen deposition, and lysyl oxidase (LOX)-mediated matrix crosslinking via epigenetic mechanisms such as histone lactylation. Building upon these mechanisms, we propose a therapeutic rationale that jointly targets mechanotransduction, aberrant metabolism, and the immunosuppressive micro-environment, and we further discuss the distinctive translational advantages of intravesical instillation for locoregional combinatorial delivery. This review aims to provide a novel conceptual framework for overcoming intravesical chemoresistance and ICI resistance in BLCA.