Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation
Abstract Triple-negative breast cancer (TNBC) continues to pose a significant obstacle in the field of oncology. Dysregulation of lipid metabolism, notably upregulated ketogenesis, has emerged as a hallmark of TNBC, yet its role in metastasis has been elusive. Here, by utilizing clinical specimens a...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Lipids in Health and Disease |
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| Online Access: | https://doi.org/10.1186/s12944-024-02364-x |
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| _version_ | 1846164912553852928 |
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| author | Haoran Jiang Yuan Zeng Xiaoye Yuan Liwen Chen Xuni Xu Xue Jiang Quan Li Gang Li Han Yang |
| author_facet | Haoran Jiang Yuan Zeng Xiaoye Yuan Liwen Chen Xuni Xu Xue Jiang Quan Li Gang Li Han Yang |
| author_sort | Haoran Jiang |
| collection | DOAJ |
| description | Abstract Triple-negative breast cancer (TNBC) continues to pose a significant obstacle in the field of oncology. Dysregulation of lipid metabolism, notably upregulated ketogenesis, has emerged as a hallmark of TNBC, yet its role in metastasis has been elusive. Here, by utilizing clinical specimens and experimental models, the study demonstrates that increased ketogenesis fosters TNBC metastasis by promoting the up-regulation of β-hydroxybutyrate (β-OHB), a key ketone body. Mechanistically, β-OHB facilitates β-hydroxybutyrylation (Kbhb) of Calpastatin (CAST), an endogenous calpain (CAPN) inhibitor, at K43, blocking the interaction with CAPN and subsequently promoting FAK phosphorylation and epithelial‒mesenchymal transition (EMT). In conclusion, the study reveals a novel regulatory axis linking ketogenesis to TNBC metastasis, shedding light on the intricate interplay between metabolic reprogramming and tumor progression. |
| format | Article |
| id | doaj-art-90a580d05b324c719707e22699cc1e0b |
| institution | Kabale University |
| issn | 1476-511X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj-art-90a580d05b324c719707e22699cc1e0b2024-11-17T12:46:16ZengBMCLipids in Health and Disease1476-511X2024-11-0123111110.1186/s12944-024-02364-xKetogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylationHaoran Jiang0Yuan Zeng1Xiaoye Yuan2Liwen Chen3Xuni Xu4Xue Jiang5Quan Li6Gang Li7Han Yang8Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Internal Medicine-Oncology, The First Affiliated Hospital of Wenzhou Medical UniversityAbstract Triple-negative breast cancer (TNBC) continues to pose a significant obstacle in the field of oncology. Dysregulation of lipid metabolism, notably upregulated ketogenesis, has emerged as a hallmark of TNBC, yet its role in metastasis has been elusive. Here, by utilizing clinical specimens and experimental models, the study demonstrates that increased ketogenesis fosters TNBC metastasis by promoting the up-regulation of β-hydroxybutyrate (β-OHB), a key ketone body. Mechanistically, β-OHB facilitates β-hydroxybutyrylation (Kbhb) of Calpastatin (CAST), an endogenous calpain (CAPN) inhibitor, at K43, blocking the interaction with CAPN and subsequently promoting FAK phosphorylation and epithelial‒mesenchymal transition (EMT). In conclusion, the study reveals a novel regulatory axis linking ketogenesis to TNBC metastasis, shedding light on the intricate interplay between metabolic reprogramming and tumor progression.https://doi.org/10.1186/s12944-024-02364-xBreast cancerMetastasisKetogenesisβ-hydroxybutyrylationEpithelial–mesenchymal transition |
| spellingShingle | Haoran Jiang Yuan Zeng Xiaoye Yuan Liwen Chen Xuni Xu Xue Jiang Quan Li Gang Li Han Yang Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation Lipids in Health and Disease Breast cancer Metastasis Ketogenesis β-hydroxybutyrylation Epithelial–mesenchymal transition |
| title | Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation |
| title_full | Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation |
| title_fullStr | Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation |
| title_full_unstemmed | Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation |
| title_short | Ketogenesis promotes triple-negative breast cancer metastasis via calpastatin β-hydroxybutyrylation |
| title_sort | ketogenesis promotes triple negative breast cancer metastasis via calpastatin β hydroxybutyrylation |
| topic | Breast cancer Metastasis Ketogenesis β-hydroxybutyrylation Epithelial–mesenchymal transition |
| url | https://doi.org/10.1186/s12944-024-02364-x |
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