title: Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.
abstract: Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib. Hepatoma cell lines PLC/PRF/5 and HepG2 were used to examine the level of plectin expression and cell migration in comparison with Chang liver cell line. In addition, sensitivity of the 3 cell lines to sorafenib treatment was also measured. Expression of plectin was lower in PLC/PRF/5 and HepG2 hepatoma cells than that of Chang liver cells whereas HepG2 and PLC/PRF/5 cells exhibit higher rate of cell migration in trans-well migration assay. Immunohistofluorecent staining on E-cadherin revealed the highest rate of collective cell migration in HepG2 cells and the lowest was found in Chang liver cells. Likewise, HepG2 cell line was most sensitive to sorafenib treatment and Chang liver cells exhibited the least sensitivity. The drug sensitivity to sorafenib treatment showed inverse correlation with the expression of plectin. We suggest that plectin deficiency and increased E-cadherin in hepatoma cells were associated with higher rates of cell motility, collective cell migration as well as higher drug sensitivity to sorafenib treatment.
authors.affiliation: a Department of Pathology , Chang Bing Show Chwan Memorial Hospital , Lugang Town , Taiwan ; Center for General Education, Providence University , Taichung City , Taiwan.
authors.forename: Chiung-Chi
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: b Department of Life Science , Tunghai University , Taichung City , Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Chao
authors.affiliation: b Department of Life Science , Tunghai University , Taichung City , Taiwan.
authors.forename: Chen-Chun
authors.initials: CC
authors.lastname: Liao
authors.affiliation: b Department of Life Science , Tunghai University , Taichung City , Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: c Department of Pathology , Kaohsiung Medical University Hospital , Kaohsiung City , Taiwan.
authors.forename: Yen-Chang Clark
authors.initials: YC
authors.lastname: Lai
authors.affiliation: d Department of Pathology , Chang Bing Show Chwan Memorial Hospital , Lugang Town , Taiwan.
authors.forename: Yih-Shyong
authors.initials: YS
authors.lastname: Lai
authors.affiliation: e Department of Pathology , Tzu Chi University Hualien City , Taiwan.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: f Department of Pathology , Chang Bing Show Chwan Memorial Hospital , Lugang Town , Taiwan ; Department of Pathology , Show Chwan Memorial Hospital , Changhua City , Taiwan , Department of Pathology , Tzu Chi University , Hualien City , Taiwan.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051190:Plectin / Q000172:deficiency*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D051190:Plectin; D047428:Protein Kinase Inhibitors; D000077157:Sorafenib
keywords: E-cadherin; collective cell migration; cytoskeleton; hepatocellular carcinoma; plectin; sorafenib