ArticleSignal transduction and targeted therapy2022
Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Fatty acid 2-hydroxylation restrains gastric cancer by blocking CD36 palmitoylation and fatty acid uptake.Oncogene · 2026Article
- Mild photothermal therapy ameliorates neurogenic bladder after sacral spinal cord injury via multi-target effects.Materials today. Bio · 2026Article
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- Intratumoral microenvironment remodeling by lncRNA ROLLCSC enhances lung adenocarcinoma progression.Genes & diseases · 2026Article
- Lipid deposition promotes YTHDF3-mediated m6A modification of PPARα to facilitate liver metastasis of colorectal cancer.Protein & cell · 2026Article
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Fatty Acid Synthase as a Potential Metabolic Vulnerability in Ocular Adnexal Sebaceous Carcinoma.Cancers · 2026Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Out"FOX"ing cancer: the implications of FOXC2 as a putative predictive biomarker for cancer immunotherapy.Frontiers in medicine · 2026Article
- Sphingolipids as indicators of exposure to long-term air pollution: a targeted metabolomics approach.Scientific reports · 2025Article
- [Plasma lipidomics-based exploration of potential biomarkers of metastasis in pediatric medulloblastoma].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Article
- Correction: Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis.Signal transduction and targeted therapy · 2025Article
- TNFα activation of the PLEKHA5-FCRLA axis disturbs lipid metabolism, leading to the progression of cutaneous malignant melanoma.Lipids in health and disease · 2025Article
- MiR-27a-5p inhibits malignant progression of differentiated thyroid cancer by directly affecting the miR-27a-5p/SREBP1 axis.Journal of endocrinological investigation · 2025Article
- KLF13 promotes esophageal cancer progression and regulates triacylglyceride and free fatty acid metabolism through GPIHBP1.Cell death & disease · 2025Article
- SLC25A1 promotes lymph node metastasis of esophageal squamous cell carcinoma by regulating lipid metabolism.International journal of oncology · 2025Article
- Identification of DownregulatedInternational journal of molecular sciences · 2025Article
- Exploring lipidomic profiles and their correlation with hormone receptor and HER2 status in breast cancer.Oncology letters · 2025Article
- Increased ACSL6 Expression Predicts a Favorable Prognosis in Triple-negative Breast Cancer.Current medicinal chemistry · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Whereas it is appreciated that cancer cells rewire lipid metabolism to survive and propagate, the roles of lipid metabolism in metastasis remain largely unknown. In this study, using esophageal squamous cell carcinoma (ESCC) as a pulmonary metastasis model, we find that the enzyme fatty acid 2-hydroxylase (FA2H), which catalyzes the hydroxylation of free fatty acids (FAs), is enriched in a subpopulation of ESCC cells with high metastatic potential, and that FA2H knockdown markedly mitigates metastatic lesions. Moreover, increased FA2H expression is positively associated with poor survival in patients with ESCC. Lipidomics analysis identifies that two dihydroceramides-Cer(d18:0/24:0) and Cer(d18:0/24:1)-are increased in FA2H-depleted metastasizing ESCC cells. Upon administration, Cer(d18:0/24:0) and Cer(d18:0/24:1) impair the formation of overt metastases in a mouse experimental metastasis model. Then, forkhead box protein C2 (FOXC2) and FA2H are found to be co-upregulated in metastatic ESCC cell populations and ESCC specimens, and FA2H expression is further experimentally verified to be transcriptionally induced by FOXC2, which is boosted per se by tumour necrosis factor α (TNFα), a critical pro-metastasis cytokine in the tumour microenvironment, in metastasizing cells. Together, these results demonstrate that TNFα-FOXC2-FA2H is a novel signaling axis to promote metastasis, and its downstream dihydroceramide products could be promising drugs to intervene in metastasis.
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