化疗
癌症
癌症研究
癌细胞
细胞凋亡
医学
程序性细胞死亡
乳腺癌
基因敲除
抗药性
结直肠癌
生物
肿瘤科
内科学
生物化学
微生物学
作者
Heng Boon Low,Zhen Lim Wong,Biao Wu,Li Ren Kong,Chin Wen Png,Yik-Lam Cho,Chunwei 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. Gascoigne,Boon Cher Goh,Ximing Xu,Yongliang Zhang
标识
DOI:10.1038/s41467-021-22638-7
摘要
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.
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