Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

作     者：Shi Qiu Yaqi Qiu Linghui Deng Ling Nie Liming Ge Xiaonan Zheng Di Jin Kun Jin Xianghong Zhou Xingyang Su Boyu Cai Jiakun Li Xiang Tu Lina Gong Liangren Liu Zhenhua Liu Yige Bao Jianzhong Ai Tianhai Lin Lu Yang Qiang Wei 

作者机构：Department of UrologyInstitute of UrologyNational Clinical Research Center for Geriatrics and Center of Biomedical Big DataWest China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Molecular OncologyInstitute of Oncology Research(IOR)Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland Department of Science and Drug TechnologyUniversity of TurinTurinItaly National Clinical Research Center of GeriatricsThe Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610000China Department of PathologyWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Pharmaceutics and BioengineeringSchool of Chemical EngineeringSichuan UniversityChengduSichuan 610000China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2024年第137卷第2期

页      面：209-221页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.81902578,81974098,8197032158) China Postdoctoral Science Foundation(No.2020M670057ZX) Programs from Science and Technology Department of Sichuan Province(No.2021YJ0462) Post-doctoral Science Research Foundation of Sichuan University(No.2020SCU12041) Post-Doctor Research Project,West China Hospital,Sichuan University(Nos.2018HXBH084,2019HXBH092) the National key research and development program of China(No.2020YFC2008601) 

主　　题：Soft tumor cells 3D Matrigel Stemness Non-muscle invasive bladder neoplasms Microfluidic analytical techniques 

摘      要：Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment *** date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer ***,the existence of soft tumor cells in bladder tumors remains ***,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer ***:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor *** patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western *** immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor ***:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer *** importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor ***,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor ***,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent ***:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and ***,the soft tumor cells become more sensitive to chemother