DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death

• DOI: 10.1038/s41467-021-22638-7
• Publication Date: 2021-04-16T11:36:09Z
• Authors: Heng Boon Low; Zhen Lim Wong; Bangyuan Wu; Li Ren Kong; Chin Wen Png; Yik-Lam Cho; Chun-Wei Li; Fengchun Xiao; Xuan Xin; Henry Yang; Jia Min Loo; Fiona Yi Xin Lee; Iain Bee Huat Tan; Ramanuj DasGupta; Han-Ming Shen; Herbert Schwarz; Nicholas R. J. Ga...; Boon Cher Goh; Xiaohong Xu; Yongliang Zhang
• Keywords: Adult; Male; MAP Kinase Signaling System; Science; 610; Antineoplastic Agents; Apoptosis; JNK PATHWAY; Cell Fractionation; Article; Disease-Free Survival; CISPLATIN; Gene Knockout Techniques; 03 medical and health sciences; SUSTAINED ACTIVATION; Cell Line, Tumor; FINGER TRANSCRIPTION FACTOR; Biomarkers, Tumor; BREAST-CANCER; Animals; Humans; Aged; DRUG-RESISTANCE; Aged, 80 and over; 0303 health sciences; Science & Technology; ACTIVATED PROTEIN-KINASES; Q; MAP KINASE; 3. Good health; Multidisciplinary Sciences; Chemotherapy, Adjuvant; Drug Resistance, Neoplasm; Gene Knockdown Techniques; Science & Technology - Other Topics; Dual-Specificity Phosphatases; Female; NASOPHARYNGEAL CARCINOMA-CELLS; SIGNALING PATHWAY; Cisplatin

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 chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant chemotherapy-induced cell death than with lower expression. Overexpression cancer leads increased upon treatment. contrast, knockdown increases their sensitivity Mechanistically, inhibits JNK p38 activation, thereby reducing BAX accumulation mitochondria reduce apoptosis. Analysis patient survival head & neck cohorts supports as marker for therapeutic outcome. This study therefore identifies prognostic efficacy chemotherapy, target overcoming chemoresistance