SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidation
Abstract Accumulating evidence has shown that the dysfunction of mitochondria, the multifunctional organelles in various cellular processes, is a pivotal event in the development of various diseases, including human cancers. Solute Carrier Family 25 Member 42 (SLC25A42) is a mitochondrial protein go...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07644-7 |
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| author | Haoying Wang Weijia Dou Mengxiao Liu Weifang Wang Ying Yang Jibin Li Zhenxiong Liu Nan Wang |
| author_facet | Haoying Wang Weijia Dou Mengxiao Liu Weifang Wang Ying Yang Jibin Li Zhenxiong Liu Nan Wang |
| author_sort | Haoying Wang |
| collection | DOAJ |
| description | Abstract Accumulating evidence has shown that the dysfunction of mitochondria, the multifunctional organelles in various cellular processes, is a pivotal event in the development of various diseases, including human cancers. Solute Carrier Family 25 Member 42 (SLC25A42) is a mitochondrial protein governing the transport of coenzyme A (CoA). However, the biological roles of SLC25A42 in human cancers are still unexplored. Here we uncovered that SLC25A42 is upregulated and correlated with a worse prognosis in GC patients. SLC25A42 promotes the proliferation of gastric cancer (GC) cells while suppresses apoptosis in vitro and in vivo. Mechanistically, SLC25A42 promotes the growth and inhibits apoptosis of GC cells by reprograming lipid metabolism. On the one hand, SLC25A42 enhances fatty acid oxidation-mediated mitochondrial respiration to provide energy for cell survival. On the other hand, SLC25A42 decreases the levels of free fatty acids and ROS to inhibit ferroptosis. Moreover, we found that SLC25A42 reprograms lipid metabolism in GC cells by upregulating the acetylation and thus the expression of CPT2. Collectively, our data reveal a critical oncogenic role of SLC25A42 in GCs and suggest that SLC25A42 represent a promising therapeutic target for GC. |
| format | Article |
| id | doaj-art-9b5f68dc39054559b0ebe8a975325c50 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-9b5f68dc39054559b0ebe8a975325c502025-08-20T03:18:23ZengNature Publishing GroupCell Death and Disease2041-48892025-04-0116111210.1038/s41419-025-07644-7SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidationHaoying Wang0Weijia Dou1Mengxiao Liu2Weifang Wang3Ying Yang4Jibin Li5Zhenxiong Liu6Nan Wang7Department of Gastroenterology, Tangdu Hospital, The Air Force Medical UniversityDepartment of Gastroenterology, Tangdu Hospital, The Air Force Medical UniversityDepartment of Gastroenterology, Xijing Hospital, The Air Force Medical UniversityState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, The Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, The Air Force Medical UniversityState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, The Air Force Medical UniversityDepartment of Gastroenterology, Tangdu Hospital, The Air Force Medical UniversityDepartment of General Surgery, Tangdu Hospital, The Air Force Medical UniversityAbstract Accumulating evidence has shown that the dysfunction of mitochondria, the multifunctional organelles in various cellular processes, is a pivotal event in the development of various diseases, including human cancers. Solute Carrier Family 25 Member 42 (SLC25A42) is a mitochondrial protein governing the transport of coenzyme A (CoA). However, the biological roles of SLC25A42 in human cancers are still unexplored. Here we uncovered that SLC25A42 is upregulated and correlated with a worse prognosis in GC patients. SLC25A42 promotes the proliferation of gastric cancer (GC) cells while suppresses apoptosis in vitro and in vivo. Mechanistically, SLC25A42 promotes the growth and inhibits apoptosis of GC cells by reprograming lipid metabolism. On the one hand, SLC25A42 enhances fatty acid oxidation-mediated mitochondrial respiration to provide energy for cell survival. On the other hand, SLC25A42 decreases the levels of free fatty acids and ROS to inhibit ferroptosis. Moreover, we found that SLC25A42 reprograms lipid metabolism in GC cells by upregulating the acetylation and thus the expression of CPT2. Collectively, our data reveal a critical oncogenic role of SLC25A42 in GCs and suggest that SLC25A42 represent a promising therapeutic target for GC.https://doi.org/10.1038/s41419-025-07644-7 |
| spellingShingle | Haoying Wang Weijia Dou Mengxiao Liu Weifang Wang Ying Yang Jibin Li Zhenxiong Liu Nan Wang SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidation Cell Death and Disease |
| title | SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidation |
| title_full | SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidation |
| title_fullStr | SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidation |
| title_full_unstemmed | SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidation |
| title_short | SLC25A42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing CPT2-mediated fatty acid oxidation |
| title_sort | slc25a42 promotes gastric cancer growth by conferring ferroptosis resistance through enhancing cpt2 mediated fatty acid oxidation |
| url | https://doi.org/10.1038/s41419-025-07644-7 |
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