DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death
| العنوان: | DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death |
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| المؤلفون: | Yongliang Zhang, Heng Boon Low, Yik-Lam Cho, Herbert Schwarz, Nicholas R. J. Gascoigne, Fengchun Xiao, Chin Wen Png, Fiona Yi Xin Lee, Xiaohong Xu, Bangyuan Wu, Jia Min Loo, Han-Ming Shen, Li Ren Kong, Henry Yang, Ramanuj DasGupta, Zhen Lim Wong, Xuan Xin, Chun-Wei Li, Boon Cher Goh, Iain Beehuat Tan |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Colorectal cancer, medicine.medical_treatment, General Physics and Astronomy, Apoptosis, Tumour biomarkers, Gene Knockout Techniques, Mice, 0302 clinical medicine, Neoplasms, bcl-2-Associated X Protein, Aged, 80 and over, Multidisciplinary, Middle Aged, Mitochondria, Cancer therapeutic resistance, Chemotherapy, Adjuvant, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Dual-Specificity Phosphatases, Female, Adult, Programmed cell death, MAP Kinase Signaling System, Science, Antineoplastic Agents, Cell Fractionation, Disease-Free Survival, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Breast cancer, Cell Line, Tumor, Biomarkers, Tumor, medicine, Animals, Humans, Aged, Chemotherapy, business.industry, Cancer, General Chemistry, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Nasopharyngeal carcinoma, Drug Resistance, Neoplasm, Cancer cell, Cancer research, Mitogen-Activated Protein Kinase Phosphatases, Cisplatin, business |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc584b47087c28dbb44baabfd0779768Test https://doaj.org/article/7cd1e1ed821d475f86d18b8927eabe0dTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fc584b47087c28dbb44baabfd0779768 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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