title: Transient knockdown-mediated deficiency in plectin alters hepatocellular motility in association with activated FAK and Rac1-GTPase.
abstract: BACKGROUND
  Plectin is one of the cytolinker proteins that play a crucial role in maintaining the integrity of cellular architecture. It is a component of desmosome complexes connecting cytoskeletal proteins and trans-membrane molecules. In epithelial cells, plectin connects cytokeratins and integrin α6β4 in hemidesmosomes anchoring to the extracellular matrix. In addition to the function of molecular adherent, plectin has been reported to exhibit functions affecting cellular signals and responsive activities mediated by stress, cellular migration, polarization as well as the dynamic movement of actin filaments. Plectin deficiency in hepatocellular carcinoma results in abnormal expression of cytokeratin 18 and disassembled hemidesmosome. Therefore, it is hypothesized that the plectin deficiency-mediated collapse of cytoskeleton may modulate cellular motility that is associated with consequent metastatic behaviors of cancer cells.
  
  
  RESULTS
  The cellular motility of plectin-deficient Chang liver cells generated by transient knockdown were analyzed by trans-well migration assay and the results revealed a higher migration rate. The confocal microscopy also demonstrated less organized and more polarized morphology as well as more focal adhesion kinase activity in comparison with that of the mock Chang liver cells. Furthermore, plectin-knockdown in Chang liver cells was associated with a higher activity of Rac1-GTPase in accordance with the results of the Rac1 pull-down assay. The immunohistochemical assay on human hepatocellular carcinoma showed that the expression of focal adhesion kinase was increased in the invasive front of tumor.
  
  
  CONCLUSIONS
  Plectin-deficient human hepatic cells exhibit higher cell motility associated with increase in focal adhesion kinase activity that are comparable to the properties of invasive hepatocellular carcinoma.
authors.affiliation: Department of Pathology, Chang Bing Show Chwan Memorial Hospital, No. 6, Lugong Rd., Lugang Town, Changhua County 505 Taiwan ; Center for General Education, Providence University, Taichung City, Taiwan.
authors.forename: Chiung-Chi
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.
authors.forename: Yen-Chang Clark
authors.initials: YC
authors.lastname: Lai
authors.affiliation: Department of Pathology, Chang Bing Show Chwan Memorial Hospital, No. 6, Lugong Rd., Lugang Town, Changhua County 505 Taiwan.
authors.forename: Yih-Shyong
authors.initials: YS
authors.lastname: Lai
authors.affiliation: Department of Pathology, Tzu Chi University, Hualien County, Taiwan.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Life Science, Tunghai University, Taichung City, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Chao
authors.affiliation: Department of Life Science, Tunghai University, Taichung City, Taiwan.
authors.forename: Kee-Chin
authors.initials: KC
authors.lastname: Sia
authors.affiliation: Department of Life Science, Tunghai University, Taichung City, Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: Department of Pathology, Chang Bing Show Chwan Memorial Hospital, No. 6, Lugong Rd., Lugang Town, Changhua County 505 Taiwan ; Department of Pathology, Tzu Chi University, Hualien County, Taiwan.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Liu
keywords: Cell motility; Cytoskeleton; Focal adhesion kinase; Hepatocellular carcinoma; Plectin