Cytoskeletal Changes in Human Transformed Cells: Studies on HOS Cells

Abstract

The cytoskeleton is the network of filaments mainly responsible for controlling and maintaining cellular morphology and motility. Three major filaments constitute the cytoskeleton and these are 1) acitn and myosin based microfilaments, 2) tubulin based microtubules and 3) intermediate filaments composed of proteins which are specific to different cell types. Since neoplastic transformation is associated with characteristic changes in cell morphology and motility, it is conceivable that there are important changes in the synthesis and organization of the cytoskeletal proteins following transformation. Indeed, microfilaments, also known as actin cables or stress fibers are known to be reorganized from a bundle state in normal cells into randomly interwoven meshwork in many transformed cells (1,2). This phenomenon, commonly referred to as diffusion of actin cable network, has been found to be a characteristic of many transformed cell lines. The mechanisms involved in the rearrangement of actin cable network are not clearly understood. However, analysis of protein differences between normal and transformed cells using quantitative two-dimensional gel electrophoretic technique has shown that the synthesis of several cytoskeletal proteins such as vimentin, tropomyosin, and a-actin is repressed in transformed cells (3–5). The fact that these cytoskeletal changes may be critical for the establishment of the transformed phenotype is underscored by the discovery of oncogenes such as v-fgr and trk which are fusions of a tyrosine kinase with γ-actin and tropomyosin genes respectively (6–11). Mutations affecting the cytosketal components such as ß and γactin, tubulin and tropomyosins have also been observed in certain cancers (9).