ArticleEBioMedicine2019
Fatty acid 2-hydroxylation inhibits tumor growth and increases sensitivity to cisplatin in gastric cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
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- HPLC-HRMS and interpretable machine learning decipher serum lipidomic signatures in NSCLC.PeerJ · 2026Article
- Advances in the Study of Metabolic Reprogramming in Gastric Cancer.Cancer medicine · 2025Review
- Cytoplasmic HuR Expression Enhances Chemoresistance in Pleural Mesothelioma Through Increased Expression of CALB2, Promotion of the E2F Pathway, and Suppression of the p53 Pathway.Thoracic cancer · 2025Article
- Prognostic significance and potential association between ALDOA and ENO1 in gastric cancer.Journal of Cancer · 2025Article
- NLRP3 promotes the proliferation and metastasis of colorectal cancer by regulating the S6K1-GLI1 signaling pathway.Journal of Cancer · 2025Article
- 2-Hydroxylation is a chemical switch linking fatty acids to glucose-stimulated insulin secretion.The Journal of biological chemistry · 2024Article
- ACAT2 suppresses the ubiquitination of YAP1 to enhance the proliferation and metastasis ability of gastric cancer via the upregulation of SETD7.Cell death & disease · 2024Article
- Prognosis significance and potential association between ALDOA and AKT expression in colorectal cancer.Scientific reports · 2024Article
- Hydroxylation of Fatty Acids by Lactic Acid Bacteria.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2023Article
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- Fatty Acid 2-Hydroxylase and 2-Hydroxylated Sphingolipids: Metabolism and Function in Health and Diseases.International journal of molecular sciences · 2023Review
- MicroRNA miR-1275 coordinately regulates AEA/LPA signals via targeting FAAH in lipid metabolism reprogramming of gastric cancer.Cell death & disease · 2023Article
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis.Signal transduction and targeted therapy · 2022Article
- STING promotes proliferation and induces drug resistance in colorectal cancer by regulating the AMPK-mTOR pathway.Journal of gastrointestinal oncology · 2022Article
- Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma.Cancers · 2022Article
- Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity.Cancer & metabolism · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMost gastric cancers are diagnosed at an advanced or metastatic stage with poor prognosis and survival rate. Fatty acid 2-hydroxylase (FA2H) with high expression in stomach generates chiral (R)-2-hydroxy FAs ((R)-2-OHFAs) and regulates glucose utilization which is important for cell proliferation and invasiveness. We hypothesized that FA2H impacts gastric tumor growth and could represent a novel target to improve gastric cancer therapy.
methodsFA2H level in 117 human gastric tumors and its association with tumor growth, metastasis and overall survival were examined. Its roles and potential mechanisms in regulating tumor growth were studied by genetic and pharmacological manipulation of gastric cancer cells in vitro and in vivo.
findingsFA2H level was lower in gastric tumor tissues as compared to surrounding tissues and associated with clinicopathologic status of patients, which were confirmed by analyses of multiple published datasets. FA2H depletion decreased tumor chemosensitivity, partially due to inhibition of AMPK and activation of the mTOR/S6K1/Gli1 pathway. Conversely, FA2H overexpression or treatment with (R)-2-OHFAs had the opposite effects. In line with these in vitro observations, FA2H knockdown promoted tumor growth with increased level of tumor Gli1 in vivo. Moreover, (R)-2-OHFA treatment significantly decreased Gli1 level in gastric tumors and enhanced tumor chemosensitivity to cisplatin, while alleviating the chemotherapy-induced weight loss in mice.
interpretationOur results demonstrate that FA2H plays an important role in regulating Hh signaling and gastric tumor growth and suggest that (R)-2-OHFAs could be effective as nontoxic wide-spectrum drugs to promote chemosensitivity. FUND: Grants of NSF, NIH, and PAPD.
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