| Literature DB >> 33863904 |
Heng Boon Low1,2, Zhen Lim Wong1,2, Bangyuan Wu1,2,3, Li Ren Kong4, Chin Wen Png1,2, Yik-Lam Cho5, Chun-Wei Li6, Fengchun Xiao7, Xuan Xin8, Henry Yang4, Jia Min Loo9, Fiona Yi Xin Lee10, Iain Bee Huat Tan10, Ramanuj DasGupta9, Han-Ming Shen5,11, Herbert Schwarz2,5, Nicholas R J Gascoigne1,2, Boon Cher Goh4,12,13, Xiaohong Xu14, Yongliang Zhang15,16.
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.Entities:
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Year: 2021 PMID： 33863904 DOI： 10.1038/s41467-021-22638-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919