Activation of SREBP-1c alters lipogenesis and promotes tumor growth and metastasis in gastric cancer - 18/06/20
, Wenjie Lu a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 11 |
| Iconographies | 5 |
| Vidéos | 0 |
| Autres | 0 |
Graphical abstract |
Highlights |
• | SREBP-1c is oncogenic via fatty acid and lipid synthesis alters lipogenesis. |
• | Fatty acid related metabolic synthetase is required for tumorigenesis. |
• | Specific fatty acid of palmitic acid is a tumor suppressor gene in fatty acid metabolism. |
• | Inhibition of SREBP-1c is a potential strategy in the treatment of Gastric cancer. |
Abstract |
Purpose |
Aggressively growing tumors are characterized by significant variations in metabolites, including lipids, and can involve the elevated synthesis ofde novo fatty acids.
Methods |
Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS)-based metabolomics and lipidomics were performed to compare human gastric cancer tissues and adjacent normal tissues from clinical patients. A series of cellular and molecular biological methods were applied to validate the lipidomics results.
Results |
Palmitic acid (PA) was found to be significantly downregulated in gastric cancer tissues, and it was found that a high concentration of PA specifically inhibited cell proliferation and impaired cell invasiveness and migrationin vitro in AGS, SGC-7901, and MGC-803 gastric cancer cell lines. Moreover, sterol regulatory element-binding protein 1 (SREBP-1c) was activated in human gastric cancer tissues, and it promoted the expression of a series of genes associated with the synthesis of fatty acids, such as SCD1 and FASN. SREBP-1c knockdown rescued the migration and invasion defects in AGS and SGC-7901 gastric cancer cells.
Conclusion |
Taken together, our findings confirmed the variation in fatty acid synthesis in gastric cancer and identified SREBP-1c as a promising target for gastric cancer treatment.
Le texte complet de cet article est disponible en PDF.Keywords : Lipidomics, Gastric cancer, SREBP-1c, Palmitic acid, Cancer therapy
Plan
Vol 128
Article 110274- août 2020 Retour au numéro
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