机构：[1]Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.[2]Immunology Programme, the Life Science Institute, National University of Singapore, Singapore, Singapore.[3]College of Life Science, China West Normal University, Nanchong, Sichuan, China.[4]Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.[5]Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.[6]Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.中山大学附属第一医院[7]Department of Pathology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.[8]Department of Mathematics, National University of Singapore, Singapore, Singapore.[9]Genome Institute of Singapore, Agency of Science Technology and Research (A*Star), Singapore, Singapore.[10]Division of Medical Oncology, National Cancer Center, Singapore, Singapore.[11]Faculty of Health Sciences, University of Macau, Macau, China.[12]Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.[13]Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.[14]Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Drug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates resistance to chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant to chemotherapy-induced cell death than cells with lower DUSP16 expression. Overexpression of DUSP16 in cancer cells leads to increased resistance to cell death upon chemotherapy treatment. In contrast, knockdown of DUSP16 in cancer cells increases their sensitivity to treatment. Mechanistically, DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria to reduce apoptosis. Analysis of patient survival in head & neck cancer and breast cancer patient cohorts supports DUSP16 as a marker for sensitivity to chemotherapy and therapeutic outcome. This study therefore identifies DUSP16 as a prognostic marker for the efficacy of chemotherapy, and as a therapeutic target for overcoming chemoresistance in cancer.
基金：
This work was supported by grants from the National Research Foundation, Prime
Minister’s Office, Singapore, under its Campus of Research Excellence and Technological
Enterprise (CREATE) program (R571-010-012-592 to Y.Z.), the Singapore National
Medical Research Council (NMRC/OFIRG/0059/2017 to Y.Z.), the NUS Global Asia
Institute (R571-000-043-133 to Y.Z.), and the National Research Foundation (NRFCRP19-2017-04 to N.R.J.G.).
第一作者机构：[1]Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.[2]Immunology Programme, the Life Science Institute, National University of Singapore, Singapore, Singapore.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.[2]Immunology Programme, the Life Science Institute, National University of Singapore, Singapore, Singapore.
推荐引用方式(GB/T 7714)：
Low Heng Boon,Wong Zhen Lim,Wu Bangyuan,et al.DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death.[J].NATURE COMMUNICATIONS.2021,12(1):doi:10.1038/s41467-021-22638-7.
APA：
Low Heng Boon,Wong Zhen Lim,Wu Bangyuan,Kong Li Ren,Png Chin Wen...&Zhang Yongliang.(2021).DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death..NATURE COMMUNICATIONS,12,(1)
MLA：
Low Heng Boon,et al."DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death.".NATURE COMMUNICATIONS 12..1(2021)
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