Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis
Summary: Succinate is a crucial metabolite in the TCA cycle and contributes to cancer development. However, the role of exogenous succinate in hepatocellular carcinoma (HCC) is unclear. Here, we report that the concentration of succinate in HCC tissues is lower compared to adjacent normal tissues, a...
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224029584 |
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| author | Shuyuan Chang Ayaka Tomii Yunfei Zhou Xun Yang Yihong Dong Jun Yan Aodi Wu Yumeng Wang Qingxin Zhang Hongxue Meng Lei Yu Wei Sun Dabin Liu |
| author_facet | Shuyuan Chang Ayaka Tomii Yunfei Zhou Xun Yang Yihong Dong Jun Yan Aodi Wu Yumeng Wang Qingxin Zhang Hongxue Meng Lei Yu Wei Sun Dabin Liu |
| author_sort | Shuyuan Chang |
| collection | DOAJ |
| description | Summary: Succinate is a crucial metabolite in the TCA cycle and contributes to cancer development. However, the role of exogenous succinate in hepatocellular carcinoma (HCC) is unclear. Here, we report that the concentration of succinate in HCC tissues is lower compared to adjacent normal tissues, as determined by spatial metabolomics and quantitative metabolomics analysis. Succinate supplementation exhibits an anti-tumorigenic effect, inhibiting cell proliferation and colony formation in liver cancer cells but not in non-tumor LO2 cells. Additionally, succinate supplementation significantly reduces tumor formation in xenograft nude mice models and carcinogen-induced WT mice models. The anti-tumorigenic function of succinate is mechanistically mediated by FN1-activated SQLE-related cholesterol biosynthesis. Our study demonstrates that exogenous succinate acts as a cholesterol biosynthesis inhibitor to suppress HCC both in vitro and in vivo, highlighting its potential therapeutic applications. |
| format | Article |
| id | doaj-art-028a7cc57ff94e21a1f42d964c1c1fcd |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-028a7cc57ff94e21a1f42d964c1c1fcd2025-01-18T05:05:05ZengElsevieriScience2589-00422025-02-01282111731Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesisShuyuan Chang0Ayaka Tomii1Yunfei Zhou2Xun Yang3Yihong Dong4Jun Yan5Aodi Wu6Yumeng Wang7Qingxin Zhang8Hongxue Meng9Lei Yu10Wei Sun11Dabin Liu12NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaDepartment of Infectious Disease, The Fourth Hospital of Harbin Medical University, Harbin 150001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, ChinaDepartment of Pathology, Harbin Medical University Cancer Hospital, Harbin, China; Corresponding authorDepartment of Infectious Disease, The Fourth Hospital of Harbin Medical University, Harbin 150001, China; Corresponding authorPeking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Corresponding authorNHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin 15001, China; Corresponding authorSummary: Succinate is a crucial metabolite in the TCA cycle and contributes to cancer development. However, the role of exogenous succinate in hepatocellular carcinoma (HCC) is unclear. Here, we report that the concentration of succinate in HCC tissues is lower compared to adjacent normal tissues, as determined by spatial metabolomics and quantitative metabolomics analysis. Succinate supplementation exhibits an anti-tumorigenic effect, inhibiting cell proliferation and colony formation in liver cancer cells but not in non-tumor LO2 cells. Additionally, succinate supplementation significantly reduces tumor formation in xenograft nude mice models and carcinogen-induced WT mice models. The anti-tumorigenic function of succinate is mechanistically mediated by FN1-activated SQLE-related cholesterol biosynthesis. Our study demonstrates that exogenous succinate acts as a cholesterol biosynthesis inhibitor to suppress HCC both in vitro and in vivo, highlighting its potential therapeutic applications.http://www.sciencedirect.com/science/article/pii/S2589004224029584Biological sciencesCell biologyCancer |
| spellingShingle | Shuyuan Chang Ayaka Tomii Yunfei Zhou Xun Yang Yihong Dong Jun Yan Aodi Wu Yumeng Wang Qingxin Zhang Hongxue Meng Lei Yu Wei Sun Dabin Liu Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis iScience Biological sciences Cell biology Cancer |
| title | Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis |
| title_full | Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis |
| title_fullStr | Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis |
| title_full_unstemmed | Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis |
| title_short | Succinate supplementation alleviates liver cancer by inhibiting the FN1/SQLE axis-mediated cholesterol biosynthesis |
| title_sort | succinate supplementation alleviates liver cancer by inhibiting the fn1 sqle axis mediated cholesterol biosynthesis |
| topic | Biological sciences Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224029584 |
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