title: Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway.
abstract: OBJECTIVE
  Altered cellular metabolism has received increased attention as an important hallmark of cancer. Activation of FASN has been found to be involved in many human tumors. Despite extensive research in FASN function on cancer, the underlying mechanism is not entirely understood yet.
  
  
  METHODS
  Cerulenin was used to suppress the FASN expression in human colorectal cancer cell lines (HT29 and LoVo). Expression of PI3K, Akt, p-Akt, mTOR, p-mTOR, FASN, and AZGP1 was measured using western blotting and qPCR. ATP and lactic acid were assessed to investigate the activation of energy metabolism. Cell cytotoxicity assay was studied by cell counting kit-8 assay. The capacity of cell proliferation and migration was investigated by clonogenic and invasion assay. Analysis of apoptosis and the cell cycle was detected by flow cytometry.
  
  
  RESULTS
  We found that the expression of FASN was down-regulated, while the expression of PI3K, p-Akt, p-mTOR, and AZGP1 was down-regulated in HT29 and LoVo cells treated with FASN inhibitor. Proliferation was reduced in FASN inhibitor-treated cells, which is consistent with an increased apoptosis rate. Furthermore, the migration of FASN inhibitor-treated cells was decreased and the content of ATP and lactic acid was also dropped.
  
  
  CONCLUSIONS
  These findings suggest that inhibited FASN suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway. The results have paved the way to understand the relations of FASN, mTOR signaling pathway, and energy metabolism in colorectal cancer cells.
authors.affiliation: Department of Internal Medicine, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Ligong
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Pathology, Jiangsu Jiankang Vocational College, Nanjing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Hematology and Oncology, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Senthilkumar
authors.affiliation: The Second Affiliated Hospital of Southeast University, Nanjing, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Internal Medicine, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
authors.affiliation: Maanshan Municipal People's Hospital, Maanshan, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Department of Internal Medicine, School of Medicine, Southeast University, Nanjing, China. seuhpl@163.com.|, Dingjia Qiao 87, Gulou District, Nanjing, 210009, China. seuhpl@163.com.
authors.forename: Peilin
authors.initials: P
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004734:Energy Metabolism; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D054890:Fatty Acid Synthase, Type I; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; C518729:FASN protein, human; C546842:MTOR protein, human
keywords: Colorectal cancer; Energy metabolism; FASN; mTOR