ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer
Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is responsible for a significant number of cancer-related deaths worldwide. Targeted drugs have been used f...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003760 |
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| author | Yang-Hsiang Lin Cheng-Yi Chen Hsiang-Cheng Chi Meng-Han Wu Ming-Wei Lai Chau-Ting Yeh |
| author_facet | Yang-Hsiang Lin Cheng-Yi Chen Hsiang-Cheng Chi Meng-Han Wu Ming-Wei Lai Chau-Ting Yeh |
| author_sort | Yang-Hsiang Lin |
| collection | DOAJ |
| description | Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is responsible for a significant number of cancer-related deaths worldwide. Targeted drugs have been used for anti-liver cancer treatment in the advanced stage, while their efficacy is greatly compromised by development of drug resistance. Drug resistance is a complicated process regulated by intrinsic and extrinsic signals and has been associated with poorer prognosis in cancer patients. In the current study, online available dataset analysis uncovered that angiopoietin-like protein 3 (ANGPTL3) manifested lower expression in sorafenib-resistant liver cancer cell lines. Additionally, ANGPTL3 was downregulated in HCC tissues, with its expression positively correlated with good prognosis. Functionally, ectopic expression of ANGPTL3 re-sensitized sorafenib-resistant cells, enhancing the sorafenib-induced reduction in cell viability and migration by suppressing zinc finger protein SNAI1 (SNAI1) expression and the protein stability of carnitine O-palmitoyltransferase 1, liver isoform (CPT1A). Clinical correlation analysis revealed that ANGPTL3 was negatively associated with SNAI1 expression. In conclusion, we identify a novel association between ANGPTL3, SNAI1 and CPT1A on sorafenib therapeutic response. Targeting ANGPTL3/SNAI1/CPT1A axis may serve as a therapeutic approach to improve prognosis of liver cancer patients with sorafenib resistance. |
| format | Article |
| id | doaj-art-dfda2c67c9c04a96ab58177b30677eb0 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-dfda2c67c9c04a96ab58177b30677eb02025-01-22T05:41:28ZengElsevierTranslational Oncology1936-52332025-02-0152102250ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancerYang-Hsiang Lin0Cheng-Yi Chen1Hsiang-Cheng Chi2Meng-Han Wu3Ming-Wei Lai4Chau-Ting Yeh5Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Corresponding authors: Liver Research Center, Chang Gung Memorial Hospital, Linkou. No 15, Wenhua 1st Rd., Guishan Dist., Taoyuan City 333, Taiwan.Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, TaiwanDepartment of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, TaiwanLiver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan, TaiwanLiver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Corresponding authors: Liver Research Center, Chang Gung Memorial Hospital, Linkou. No 15, Wenhua 1st Rd., Guishan Dist., Taoyuan City 333, Taiwan.Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is responsible for a significant number of cancer-related deaths worldwide. Targeted drugs have been used for anti-liver cancer treatment in the advanced stage, while their efficacy is greatly compromised by development of drug resistance. Drug resistance is a complicated process regulated by intrinsic and extrinsic signals and has been associated with poorer prognosis in cancer patients. In the current study, online available dataset analysis uncovered that angiopoietin-like protein 3 (ANGPTL3) manifested lower expression in sorafenib-resistant liver cancer cell lines. Additionally, ANGPTL3 was downregulated in HCC tissues, with its expression positively correlated with good prognosis. Functionally, ectopic expression of ANGPTL3 re-sensitized sorafenib-resistant cells, enhancing the sorafenib-induced reduction in cell viability and migration by suppressing zinc finger protein SNAI1 (SNAI1) expression and the protein stability of carnitine O-palmitoyltransferase 1, liver isoform (CPT1A). Clinical correlation analysis revealed that ANGPTL3 was negatively associated with SNAI1 expression. In conclusion, we identify a novel association between ANGPTL3, SNAI1 and CPT1A on sorafenib therapeutic response. Targeting ANGPTL3/SNAI1/CPT1A axis may serve as a therapeutic approach to improve prognosis of liver cancer patients with sorafenib resistance.http://www.sciencedirect.com/science/article/pii/S1936523324003760Hepatocellular carcinomaANGPTL3sorafenibCPT1AProtein stability |
| spellingShingle | Yang-Hsiang Lin Cheng-Yi Chen Hsiang-Cheng Chi Meng-Han Wu Ming-Wei Lai Chau-Ting Yeh ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer Translational Oncology Hepatocellular carcinoma ANGPTL3 sorafenib CPT1A Protein stability |
| title | ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer |
| title_full | ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer |
| title_fullStr | ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer |
| title_full_unstemmed | ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer |
| title_short | ANGPTL3 overcomes sorafenib resistance via suppression of SNAI1 and CPT1A in liver cancer |
| title_sort | angptl3 overcomes sorafenib resistance via suppression of snai1 and cpt1a in liver cancer |
| topic | Hepatocellular carcinoma ANGPTL3 sorafenib CPT1A Protein stability |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003760 |
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