title: Increased expression of S100A6 promotes cell proliferation and migration in human hepatocellular carcinoma.
abstract: High levels of S100A6 have been associated with poor outcome in some types of human cancers, but the role of S100A6 in the molecular pathogenesis of these cancers is largely unknown. This study was performed to explore the expression and functional roles of S100A6 in hepatocellular carcinoma (HCC). The expression level of S100A6 in HCC tumor and corresponding peritumoral tissues were determined by immunohistochemistry analysis. The potential functions of S100A6 in tumorigenesis and metastasis were analyzed by cell proliferation, migration, and invasion assays in human liver cancer cells. Moreover, through expression and purification of S100A6 recombinant protein tagged with cell-penetrating peptide, we analyzed its complex extracellular/intracellular effects in a S100A6-silenced cellular model. As a result, the expression of S100A6 was up-regulated in human HCC compared with adjacent peritumoral tissues. S100A6 silencing inhibited the growth and motility of HCC cells, while intracellular re-expression of S100A6 could rescue the proliferation and migration defects. Intracellular over-expression of S100A6 resulted in down-regulation of E-cadherin expression and promoted nuclear accumulation of β-catenin. Moreover, we found that the enhanced cell proliferation and motility after S100A6 stimulation were dependent on the activation of PI3K/AKT pathway. These results suggest that S100A6 may be involved in promotion and progression of human liver cancer.
  
  
  CONCLUSIONS
  S100A6 is overexpressed in human hepatocellular carcinoma clinical specimens. S100A6 promotes proliferation and migration of human hepatoma cells. Overexpression of S100A6 results in alteration of E-cadherin and β-catenin. The multi-effects of S100A6 may be mediated in part by PI3K/AKT pathway activation.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China, ziqiangli21@gmail.com.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Tang
authors.forename: Bo
authors.initials: B
authors.lastname: Ling
authors.forename: Shiying
authors.initials: S
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Chunlai
authors.initials: C
authors.lastname: Nie
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yuan
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Aiping
authors.initials: A
authors.lastname: Tong
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000473:pathology; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013752:Tetracycline / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; D051176:beta Catenin; C055351:S100A6 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013752:Tetracycline