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DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death
Low, Heng Boon1,2; Wong, Zhen Lim1,2; Wu, Bangyuan1,2,3; Kong, Li Ren4; Png, Chin Wen1,2; Cho, Yik Lam5; Li, Chun Wei6; Xiao, Fengchun7; Xin, Xuan8; Yang, Henry4; Loo, Jia Min9; Lee, Fiona Yi Xin10; Tan, Iain Bee Huat10; DasGupta, Ramanuj9; Shen, Han Ming5,11; Schwarz, Herbert2,5; Gascoigne, Nicholas R.J.1,2; Goh, Boon Cher4,12,13; Xu, Xiaohong14; Zhang, Yongliang1,2
2021-12-01
Source PublicationNature Communications
ISSN2041-1723
Volume12Issue:1
Abstract

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.

DOI10.1038/s41467-021-22638-7
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000641847400006
Scopus ID2-s2.0-85104442533
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorZhang, Yongliang
Affiliation1.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, 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
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
Recommended Citation
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).
APA Low, Heng Boon,Wong, Zhen Lim,Wu, Bangyuan,Kong, Li Ren,Png, Chin Wen,Cho, Yik Lam,Li, Chun Wei,Xiao, Fengchun,Xin, Xuan,Yang, Henry,Loo, Jia Min,Lee, Fiona Yi Xin,Tan, Iain Bee Huat,DasGupta, Ramanuj,Shen, Han Ming,Schwarz, Herbert,Gascoigne, Nicholas R.J.,Goh, Boon Cher,Xu, Xiaohong,&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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