title: mTOR signaling pathway is a target for the treatment of colorectal cancer.
abstract: BACKGROUND
  mTOR signaling has been suggested to be an important factor involved in tumorigenesis, but its role in human colorectal cancer (CRC) has not been completely elucidated. Herein, the purpose of this study was to analyze the distribution pattern of mTOR signaling components in CRC and adenoma and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for CRC.
  
  
  METHODS
  Immunohistochemical analysis was performed on human CRC and adenoma for mTOR signaling components, including mTOR, p70s6 K, and 4EBP1. HCT116 and SW480 human CRC cell lines were treated with siRNA directed against mTOR, and cell viability, cell cycle, and apoptosis were assessed. HCT116 and SW480 cells were injected into athymic nude mice to establish a CRC xenograft model. Mice were randomly transfected with either nontargeting control or mTOR siRNA, and tumor volume, mTOR signaling activity, and apoptosis were evaluated.
  
  
  RESULTS
  mTOR signaling components, including mTOR, p70s6 K, and 4EBP1, were highly activated in glandular elements of CRC and colorectal adenomas with high-grade intraepithelial neoplasia (HIN), with a correlation between staining intensity and depth of infiltration in CRC. Inhibition of mTOR expression using a specific mTOR siRNA resulted in considerably decreased in vitro and in vivo cell growth.
  
  
  CONCLUSIONS
  mTOR signaling is associated with the clinical pathological parameters of human CRC. siRNA-mediated gene silencing of mTOR may be a novel therapeutic strategy for CRC.
authors.affiliation: Shanghai Institute of Digestive Disease, Shanghai Jiaotong University School of Medicine Renji Hospital, Shanghai, China.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dai
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Xiong
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tian
authors.forename: Feng-Hou
authors.initials: FH
authors.lastname: Gao
authors.forename: Mang-Hua
authors.initials: MH
authors.lastname: Xu
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Ze-Guang
authors.initials: ZG
authors.lastname: Han
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D012007:Rectum / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases