title: Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway.
abstract: Fatty acid synthase (Fasn) is the key metabolic enzyme that accounts for the terminal catalytic step in fatty acid synthesis, which is hyperactivated in various tumors. In this study, we depicted that Fasn expression was elevated in human colorectal cancer (CRC), which accordingly led to lymphatic and distant metastasis and a more advanced clinical phenotype. Genetic perturbations demonstrated that knocking down Fasn inhibited cell migration and invasion both in SW480 and HT29 CRC cell lines. Further mechanical exploration revealed that Fasn knockdown could attenuate Wnt signaling pathway via downregulating distinctive genes, namely Wnt5a, Wnt5b, Fzd2, which at least partly contributed to the decrease in metastasis. Clinical evidence verified a positive correlation between Fasn expression and Wnt signal marker gene expression in a cohort of 43 CRC patients. In conclusion, we shed light on metabolic switches took place during CRC carcinogenesis, among which Fasn is a critical factor and a potential therapeutic target.
authors.affiliation: Department of general surgery, Zhongshan hospital, Fudan university, Shanghai, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of general surgery, Zhongshan hospital, Fudan university, Shanghai, China.
authors.forename: Qiulei
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Department of general surgery, Zhongshan hospital, Fudan university, Shanghai, China.
authors.forename: Guohao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D060449:Wnt Signaling Pathway
chemical_list: C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D064429:Fatty Acid Synthases
keywords: Colorectal carcinoma; Wnt signaling; fatty acid synthase; metastasis