title: Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer.
abstract: Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan-Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDAC patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC.
authors.affiliation: Department of Science and Technology, Nanjing University of Chinese Medicine, 210023, PR China. Electronic address: drbiany@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Bian
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, 210023, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Science and Technology, Nanjing University of Chinese Medicine, 210023, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Science and Technology, Nanjing University of Chinese Medicine, 210023, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D064429:Fatty Acid Synthases / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D064429:Fatty Acid Synthases; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: EGFR; FASN; Growth; Pancreatic cancer