Liu Yi-Hsiang, Cheng Chiung-Chi, Ho Chin-Chin, Chao Wei-Ting, Pei Ren-Jeng, Hsu Yung-Hsiang, Ho Lu-Chang, Shiu Bei-Hao, Lai Yih-Shyong
Department of Pathology, Kuang Tien General Hospital, Dajia, Taichung, Taiwan.
Med Mol Morphol. 2011 Mar;44(1):21-6. doi: 10.1007/s00795-010-0499-y.
Plectin is a versatile cytoplasmic cross-linking protein that connects intermediate filaments to microfilaments, microtubules, and membrane adhesion sites. The cross-linking functions of plectin help organize the cytoskeleton into a stable meshwork important for maintaining uniformity in cell size and shape. As cells of hepatocellular carcinoma are morphologically different from normal human hepatocytes, we hypothesized that altered plectin expression and cytoskeletal organization underlies this pleomorphic transformation. To test this hypothesis, we analyzed expression levels and organization of all cytoskeletal elements, including intermediate filaments, microfilaments, and microtubules, after plectin knockdown in human Chang liver cells. We found that expression of cytokeratin 18, but not actin or tubulin, was downregulated by suppression of plectin protein. Furthermore, cytokeratin networks were partially collapsed and actin-rich stress fibers were increased. The organization of microtubule networks, by contrast, was unaltered. These findings support our hypothesis that, via effects on cytoskeletal organization, plectin deficiency might play an important role in the transformation of human liver cells.
网蛋白是一种多功能的细胞质交联蛋白，它将中间丝与微丝、微管和膜粘附位点连接起来。网蛋白的交联功能有助于将细胞骨架组织成一个稳定的网络，这对于维持细胞大小和形状的均匀性很重要。由于肝癌细胞在形态上与正常人类肝细胞不同，我们推测网蛋白表达和细胞骨架组织的改变是这种多形性转变的基础。为了验证这一假设，我们在人张氏肝癌细胞中网蛋白敲低后，分析了所有细胞骨架成分的表达水平和组织情况，包括中间丝、微丝和微管。我们发现，抑制网蛋白的表达会下调细胞角蛋白18的表达，但不会影响肌动蛋白或微管蛋白的表达。此外，细胞角蛋白网络部分塌陷，富含肌动蛋白的应力纤维增加。相比之下，微管网络的组织没有改变。这些发现支持了我们的假设，即通过对细胞骨架组织的影响，网蛋白缺乏可能在人类肝细胞的转变中起重要作用。
