DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Nature communications - 12(2021), 1 vom: 16. Apr., Seite 2284 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Low, Heng Boon [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.05.2021 Date Revised 31.01.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-021-22638-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324185901 |
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| 245 | 1 | 0 | |a DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death |
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| 500 | |a Date Revised 31.01.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a BAX protein, human |2 NLM | |
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| 700 | 1 | |a Wong, Zhen Lim |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Bangyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Li Ren |e verfasserin |4 aut | |
| 700 | 1 | |a Png, Chin Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Yik-Lam |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chun-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Fengchun |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Henry |e verfasserin |4 aut | |
| 700 | 1 | |a Loo, Jia Min |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Fiona Yi Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Iain Bee Huat |e verfasserin |4 aut | |
| 700 | 1 | |a DasGupta, Ramanuj |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Han-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Schwarz, Herbert |e verfasserin |4 aut | |
| 700 | 1 | |a Gascoigne, Nicholas R J |e verfasserin |4 aut | |
| 700 | 1 | |a Goh, Boon Cher |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiaohong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yongliang |e verfasserin |4 aut | |
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