title: Loss of fatty acid synthase inhibits the "HER2-PI3K/Akt axis" activity and malignant phenotype of Caco-2 cells.
abstract: BACKGROUND
  Fatty acid synthase (FASN) is frequently activated and overexpressed in human cancers, and plays a crucial role in the carcinogenesis of various cancers. In this study, our aims were to explore the role of FASN in regulating the "HER2-PI3K/Akt axis" activity and malignant phenotype of colorectal cancer.
  
  
  METHODS
  Caco-2 cells with a high expression of both HER2 and FASN were selected for functional characterization. Caco-2 cells were transfected with either the FASN specific RNAi plasmid or the negative control RNAi plasmid, followed by the RT-qPCR and western blot to examine the expression of FASN, HER2, PI3K and Akt. The MTT and colony formation assays were used to assess the proliferation potential. The migration was investigated by the transwell, and the apoptosis and cell cycle were assayed by the flow cytometry.
  
  
  RESULTS
  Notably, the expression of FASN, HER2, PI3K and Akt were downregulated upon a silence of FASN. The proliferation was decreased after a downregulation of FASN, which was consistent with an increased apoptosis rate. The migration was also impaired in FASN-silenced cells.
  
  
  CONCLUSIONS
  A downregulation of FASN effectively inhibits the activity of "HER2-PI3K/Akt axis" and alters the malignant phenotype in colorectal cancer cells.
authors.affiliation: Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, Peoples R China. linan0627@yahoo.cn
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Heng
authors.initials: H
authors.lastname: Lu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Bu
authors.forename: Peilin
authors.initials: P
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D018938:Caco-2 Cells; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D053492:Elafin / Q000096:biosynthesis* / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000378:metabolism; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053492:Elafin; D054890:Fatty Acid Synthase, Type I; D051058:Oncogene Protein v-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C506806:PI3 protein, human; C518729:FASN protein, human; C508053:ERBB2 protein, human