Cancer Cytoskeleton Research Articles

Protected cytoskeletal-related proteins: Towards a resolution of contradictions regarding the role of the cytoskeleton in cancer.

Initial reports of the role of the cytoskeleton in cancer indicated that tumor cells with a more disorganized cytoskeleton were more tumorigenic. These reports were based on stains for the F-actin cytoskeleton, for example, using phalloidin or anti-F-actin antibody reagents, and gave a basic impression of F-actin-based cytoskeletal integrity. Later developments emphasized the significance of the cytoskeletal elements in cell migration, presumably associated with either basement membrane invasion or metastasis, or both, with several specific proteins implicated in the formation of cell invadopodia. With the advent of genomics approaches, it has become clear that cytoskeletal related proteins are indeed common targets of mutagenesis in cancer and commonly rank among the most mutated proteins in cancers, presumably due to large coding region sizes and the significant stochastic component to human mutagenesis. This cytoskeletal genomics result is consistent with the loss of cytoskeleton integrity as a hallmark of tumor development, but raises the question of whether such mutational sensitivity relates to the migration and invadopodia aspects of tumor progression. In the present study, the authors report that it is possible to identify a set of cytoskeletal related proteins protected from mutation, in comparison to the commonly mutated cytoskeleton related proteins in certain, but not all cancer, datasets.

Validation of an Algorithm to Quantify Changes in Actin Cytoskeletal Organization

The actin cytoskeleton plays an important role in most, if not all, processes necessary for cell survival. Given the fundamental role that the actin cytoskeleton plays in the progression of cancer, it is an ideal target for chemotherapy. Although it is possible to image the actin cytoskeleton in a high-throughput manner, there is currently no validated method to quantify changes in the cytoskeleton in the same capacity, which makes research into its organization and the development of anticytoskeletal drugs difficult. We have validated the use of a linear feature detection algorithm, allowing us to measure changes in actin filament organization. Its ability to quantify changes associated with cytoskeletal disruption will make it a valuable tool in the development of compounds that target the cytoskeleton in cancer. Our results show that this algorithm can quantify cytoskeletal changes in a cell-based system after addition of both well-established and novel anticytoskeletal agents using either fluorescence microscopy or a high-content imaging approach. This novel method gives us the potential to screen compounds in a high-throughput manner for cancer and other diseases in which the cytoskeleton plays a key role.

Actin-based biomechanical features of suspended normal and cancer cells

The mechanical features of individual cells have been regarded as unique indicators of their states, which could constantly change in accordance with cellular events and diseases. Particularly, cancer progression was characterized by the disruption and/or reorganization of actin filaments causing mechanical changes. Thus, mechanical characterization of cells could become an effective cytotechnological approach for early detection of cancer. To develop mechanical cytotechnology, it would be necessary to clarify the mechanical properties in various cell adhesion states. In this study, we investigated the surface mechanical behavior of cancer and normal cells in the adherent and suspended states using atomic force microscopy. Adherent normal stromal cells showed high surface stiffness due to developed actin cap structures on their apical surface, whereas cancer cells did not have developed filamentous actin structures, and their surface stiffness was low. Upon cell detachment from the substrate, filamentous actin structures of adherent normal stromal cells reorganized to the cortical region and their surface stiffness decreased consequently however, the stiffness of suspended normal cells remained higher than that of cancer cells. These suspended state actin structures were similar, regardless of the cell type. Furthermore, the mechanical responses of the cancer and normal stromal cells to perturbation of the actin cytoskeleton were different, suggesting distinct regulatory mechanisms for actin cytoskeleton in cancer and normal cells in both adherent and suspended states. Therefore, cancer cells possess specific mechanical and actin cytoskeleton features different from normal stromal cells.