FASN (fatty acid synthase) is a large, multidomain, lipogenic protein. It is composed of seven catalytic domains, which include β-ketoacyl synthase (KS), malonyl acetyl transferase, dehydratase (DH), enoyl-acyl carrier protein-reductase (ER), β-ketoacyl reductase (KR), acyl carrier protein (ACP), and thioesterase domains. This protein exists in a functionally homodimeric form. Under normal conditions, it is expressed at low levels.
FASN (fatty acid synthase) is responsible for the biogenesis of long chain saturated fatty acids, which make up lipid signaling molecules, membranes and anchors for membrane proteins. This protein is linked to multiple disorders such as, hepatic steatosis, cancer, inflammation, obesity and diabetes. It is highly up-regulated in multiple cancers such as, breast, lung, prostate, colon, pancreatic and bladder. In breast cancer, this protein controls liver fatty acid-binding protein (L-FABP), vascular endothelial growth factor (VEGF) and VEGF Receptor-2 (VEGFR2), thus, promoting epithelial-mesenchymal transition of breast cancer cells. Trastuzumab-resistance in breast cancer is mediated by the up-regulation of FASN by Pin-1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) protein. It is up-regulated in malignant gliomas, and might have potential as a therapeutic target for the drug Orlistat.
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