DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer
Abstract. Ferroptosis is a oxidative damage-dependent form of regulated cell death that has become an emerging target for disease prevention and treatment. Here, we show that dual-specificity phosphatase 1 (DUSP1), a phosphatase playing multiple roles in stress-signaling pathways, is a new repressor...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2020-09-01
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| Series: | Journal of Pancreatology |
| Online Access: | http://journals.lww.com/10.1097/JP9.0000000000000054 |
| _version_ | 1818738513057677312 |
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| author | Yangchun Xie Feimei Kuang Jiao Liu Daolin Tang, MD Rui Kang |
| author_facet | Yangchun Xie Feimei Kuang Jiao Liu Daolin Tang, MD Rui Kang |
| author_sort | Yangchun Xie |
| collection | DOAJ |
| description | Abstract. Ferroptosis is a oxidative damage-dependent form of regulated cell death that has become an emerging target for disease prevention and treatment. Here, we show that dual-specificity phosphatase 1 (DUSP1), a phosphatase playing multiple roles in stress-signaling pathways, is a new repressor of ferroptosis in human pancreatic cancer cells. Several classical ferroptosis activators (eg, erastin and RSL3) induce the expression of DUSP1, but not other members of DUSP, which depends on extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Moreover, shRNA-mediated DUSP1 knockdown increases the anticancer activity of ferroptosis activators in pancreatic cancer cells through activating lipid peroxidation in vitro and in vivo. Importantly, DUSP1-mediated autophagy is responsible for lipid peroxidation-mediated ferroptotic cell death. Thus, the DUSP1-related ferroptotic pathway may represent a potential target for therapeutic intervention in pancreatic cancer. |
| first_indexed | 2024-12-18T01:10:08Z |
| format | Article |
| id | doaj.art-692a4ef90e154584b3efeda4824a0466 |
| institution | Directory Open Access Journal |
| issn | 2096-5664 2577-3577 |
| language | English |
| last_indexed | 2024-12-18T01:10:08Z |
| publishDate | 2020-09-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Journal of Pancreatology |
| spelling | doaj.art-692a4ef90e154584b3efeda4824a04662022-12-21T21:26:07ZengWolters Kluwer Health/LWWJournal of Pancreatology2096-56642577-35772020-09-013315416010.1097/JP9.0000000000000054202009000-00006DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancerYangchun XieFeimei KuangJiao LiuDaolin Tang, MDRui KangAbstract. Ferroptosis is a oxidative damage-dependent form of regulated cell death that has become an emerging target for disease prevention and treatment. Here, we show that dual-specificity phosphatase 1 (DUSP1), a phosphatase playing multiple roles in stress-signaling pathways, is a new repressor of ferroptosis in human pancreatic cancer cells. Several classical ferroptosis activators (eg, erastin and RSL3) induce the expression of DUSP1, but not other members of DUSP, which depends on extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Moreover, shRNA-mediated DUSP1 knockdown increases the anticancer activity of ferroptosis activators in pancreatic cancer cells through activating lipid peroxidation in vitro and in vivo. Importantly, DUSP1-mediated autophagy is responsible for lipid peroxidation-mediated ferroptotic cell death. Thus, the DUSP1-related ferroptotic pathway may represent a potential target for therapeutic intervention in pancreatic cancer.http://journals.lww.com/10.1097/JP9.0000000000000054 |
| spellingShingle | Yangchun Xie Feimei Kuang Jiao Liu Daolin Tang, MD Rui Kang DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer Journal of Pancreatology |
| title | DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer |
| title_full | DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer |
| title_fullStr | DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer |
| title_full_unstemmed | DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer |
| title_short | DUSP1 Blocks autophagy-dependent ferroptosis in pancreatic cancer |
| title_sort | dusp1 blocks autophagy dependent ferroptosis in pancreatic cancer |
| url | http://journals.lww.com/10.1097/JP9.0000000000000054 |
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