Haoran Jiang, Yuan Zeng, Xiaoye Yuan, Liwen Chen, Xuni Xu, Xue Jiang, Quan Li, Gang Li, Han Yang
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引用次数: 0
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.
期刊介绍：
Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds.
Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.
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