title: Caveolin-1 Confers Resistance of Hepatoma Cells to Anoikis by Activating IGF-1 Pathway.
abstract: OBJECTIVE
  Anoikis resistance is a prerequisite for hepatocellular carcinoma (HCC) metastasis. The role of Caveolin-1 (CAV1) in anoikis resistance of HCC remains unclear.
  
  
  METHODS
  The oncogenic effect of CAV1 on anchor-independent growth and anoikis resistance was investigated by overexpression and knockdown of CAV1 in hepatoma cells. IGF-1 pathway and its downstream signals were detected by immunoblot analysis. Caveolae invagination and IGF-1R internalization was studied by electron microscopy and (125)I-IGF1 internalization assay, respectively. The role of IGF-1R and tyrosine-14 residue (Y-14) of CAV1 was explored by deletion experiment and mutation experiment, respectively. The correlation of CAV1 and IGF-1R was further examined by immunochemical analysis in 120 HCC specimens.
  
  
  RESULTS
  CAV1 could promote anchor-independent growth and anoikis resistance in hepatoma cells. CAV1-overexpression increased the expression of IGF-1R and subsequently activated PI3K/Akt and RAF/MEK/ERK pathway, while CAV1 knockdown showed the opposite effect. The mechanism study revealed that CAV1 facilitated caveolae invagination and (125)I-IGF1 internalization. IGF-1R deletion or Y-14 mutation reversed CAV1 mediated anchor-independent growth and anoikis resistance. In addition, CAV1 expression was positively related to IGF-1R expression in human HCC tissues.
  
  
  CONCLUSIONS
  CAV1 confers resistance of hepatoma cells to anoikis by activating IGF-1 pathway, providing a potential therapeutic target for HCC metastasis.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Tang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Feng
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Ren
authors.forename: Yinkun
authors.initials: Y
authors.lastname: Liu
authors.forename: Biwei
authors.initials: B
authors.lastname: Yang
authors.forename: Bei
authors.initials: B
authors.lastname: lv
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.forename: Jinglin
authors.initials: J
authors.lastname: Xia
authors.forename: Ningling
authors.initials: N
authors.lastname: Ge
mesh_terms: D023102:Anoikis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D021941:Caveolae / Q000378:metabolism / Q000473:pathology; D051242:Caveolin 1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases