title: A high level of integrin α6 expression in human intrahepatic cholangiocarcinoma cells is associated with a migratory and invasive phenotype.
abstract: BACKGROUND
  The integrin α6 subunit is part of the integrin α6β1 and α6β4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed.
  
  
  METHODS
  Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated.
  
  
  RESULTS
  The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p < 0.05). The postoperative 5-year overall survival (OS) rate in patients with integrin α6(low) was higher than that of the integrin α6(high) group.
  
  
  CONCLUSIONS
  Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC.
authors.affiliation: Department of Gastroenterology, Yangzhou No. 1 People's Hospital, The Second Clinical School of Yangzhou University, Yangzhou, 225000, People's Republic of China. ybding66@163.com
authors.forename: Yan-bing
authors.initials: YB
authors.lastname: Ding
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.forename: You-sheng
authors.initials: YS
authors.lastname: Huang
authors.forename: Wei-ming
authors.initials: WM
authors.lastname: Xiao
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Yuan-zhi
authors.initials: YZ
authors.lastname: Wang
authors.forename: Da-cheng
authors.initials: DC
authors.lastname: Wu
authors.forename: Guo-tao
authors.initials: GT
authors.lastname: Lu
authors.forename: Ke-yan
authors.initials: KY
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D039503:Integrin alpha6 / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D039503:Integrin alpha6