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- Title
DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death.
- Authors
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
- 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. Chemoresistance is one of the main challenges for cancer therapy success. Here, the authors show that dual-specificity phosphatase 16 (DUSP16) expression is associated with chemoresistance in several types of cancer through impairing mitochondria-associated apoptosis.
- Subjects
CELL death; CELLULAR control mechanisms; HEAD &; neck cancer; DRUG resistance in cancer cells; COLORECTAL cancer
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22638-7