title: Cytokeratin 18-mediated disorganization of intermediate filaments is induced by degradation of plectin in human liver cells.
abstract: Plectin is a cross-linking protein that organizes the cytoskeleton into a stable meshwork that helps maintain the uniform size and shape of cells. As cells of hepatocellular carcinoma are morphologically different from healthy human hepatocytes, we hypothesized that plectin deficiency and cytoskeletal disorganization underlies this pleomorphic transformation. To test this hypothesis we induced apoptosis as the most accessible pathway for creating plectin deficiency status in vivo. We analyzed expression levels and organization of plectin and other cytoskeletal elements, including intermediate filaments, microfilaments, and microtubules, after staurosporine-induced apoptosis in human Chang liver cells. The results revealed the expression of plectin and cytokeratin 18 were downregulated in hepatocellular carcinoma tissues in vivo. The expression of actin and tubulin, however, were not altered. In vitro analysis indicated that plectin and cytokeratin 18 were cleaved following staurosporine-treatment of human Chang liver cells. Time course experiments revealed that plectin was cleaved 2h earlier than cytokeratin 18. The organization of plectin and cytokeratin 18 networks collapsed after staurosporine-treatment. Conclusively, degradation of plectin induced by staurosporine-treatment in liver cells resulted in cytoskeleton disruption and induced morphological changes in these cells by affecting the expression and organization of cytokeratin 18.
authors.affiliation: Department of Pathology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Liu
authors.forename: Chin-Chin
authors.initials: CC
authors.lastname: Ho
authors.forename: Chiung-Chi
authors.initials: CC
authors.lastname: Cheng
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Chao
authors.forename: Ren-Jeng
authors.initials: RJ
authors.lastname: Pei
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.forename: Yih-Shyong
authors.initials: YS
authors.lastname: Lai
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D053538:Keratin-18 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D051190:Plectin / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D053538:Keratin-18; D051190:Plectin; D019311:Staurosporine