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Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Wang Manli[1] ; Chen Xuelan[2] ; Tan Ping[1] ; Wang Yiyun[2] ; Pan Xiangyu[2] ; Lin Tianhai[1] ; Jiang Yong[3] ; Wang Bo[2] ; Xu Huan[3] ; Wang Yuying[2] ; Yang Yucen[2] ; Wang Jian[2] ; Zhao Lei[2] ; Zhang Jiapeng[1] ; Zhong Ailing[2] ; Peng Yiman[2] ; Du Jiajia[2] ; Zhang Qi[2] ; Zheng Jianan[2] ; Chen Jingyao[2] ; Dai Siqi[2] ; Na Feifei[4] ; Lu Zhenghao[5] ; Liu Jiaming[1] ; Zheng Xiaonan[1] ; Yang Lu[1] ; Zhang Peng[1] ; Han Ping[1] ; Gong Qiyong[6,7] ; Zhong Qian[8] ; Xiao Kai[9] ; Yang Hanshuo[2] ; Deng Hongxin[2] ; Zhao Yinglan[2] ; Shi Hubing[2] ; Man Jianghong[10] ; Gou Maling[2] ; Zhao Chengjian[2] ; Dai Lunzhi[2] ; Xue Zhihong[2] ; Chen Lu[2] ; Wang Yuan[2] ; Zeng Musheng[8] ; Huang Canhua[2] ; Wei Qiang[1] ; Wei Yuquan[2] ; Liu Yu[2] ; Chen Chong[1] ;
机构： [1]Department of Urology, Institute of Urology, State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu,Sichuan 610041, China [2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China [3]Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China [4]Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University,Chengdu, Sichuan 610041, China [5]Chengdu OrganoidMed Medical Laboratory, West China Health Valley, Chengdu, Sichuan 610041, China [6]Huaxi MRResearch Center (HMRRC), Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China [7]Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan 610041, China [8]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory ofNasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510000, China [9]Laboratory of Non-Human Primate Disease Model Research, State Key Laboratory of Biotherapy, Collaborative Innovation Center forBiotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [10]State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing 100850, China
出处：
DOI： 10.1016/j.ccell.2022.08.010
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摘要：
Cisplatin-based chemotherapy remains the primary treatment for unresectable and metastatic muscle-invasive bladder cancers (MIBCs). However, tumors frequently develop chemoresistance. Here, we established a primary and orthotopic MIBC mouse model with gene-edited organoids to recapitulate the full course of chemotherapy in patients. We found that partial squamous differentiation, called semi-squamatization, is associated with acquired chemoresistance in both mice and human MIBCs. Multi-omics analyses showed that cathepsin H (CTSH) is correlated with chemoresistance and semi-squamatization. Cathepsin inhibition by E64 treatment induces full squamous differentiation and pyroptosis, and thus specifically restrains chemoresistant MIBCs. Mechanistically, E64 treatment activates the tumor necrosis factor pathway, which is required for the terminal differentiation and pyroptosis of chemoresistant MIBC cells. Our study revealed that semi-squamatization is a type of lineage plasticity associated with chemoresistance, suggesting that differentiation via targeting of CTSH is a potential therapeutic strategy for the treatment of chemoresistant MIBCs.Copyright © 2022 Elsevier Inc. All rights reserved.

基金：
National Key R&D Program of China (2017YFA0505600); the National Natural Science Foundation of China (82130007, 82170171, 82002692, 81770157, and 81522003); the Post- Doctoral Research Project of Sichuan University (grant no. 2021SCU12016); the Post-Doctoral Research Project, West China Hospital, Sichuan University (grant no. 19HXBH057); the ‘‘1.3.5’’ Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21009, ZYYC20004, ZYGD18011, and ZY2016104); and the Sichuan Science and Technology Program (2020YFQ0059 and 2018JZ0077).
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 肿瘤学 1 区 细胞生物学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 细胞生物学 1 区 肿瘤学
JCR分区：
出版当年[2022]版：
Q1 CELL BIOLOGY Q1 ONCOLOGY
最新[2023]版：
Q1 CELL BIOLOGY Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Department of Urology, Institute of Urology, State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu,Sichuan 610041, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Wang Manli,Chen Xuelan,Tan Ping,et al.Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer[J].CANCER CELL.2022,40(9):1044-+.doi:10.1016/j.ccell.2022.08.010.
APA：
Wang Manli,Chen Xuelan,Tan Ping,Wang Yiyun,Pan Xiangyu...&Chen Chong.(2022).Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer.CANCER CELL,40,(9)
MLA：
Wang Manli,et al."Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer".CANCER CELL 40..9(2022):1044-+

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