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

Abstract

Abstract. 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.

Cytoskeletal Proteins in Cancer and Intracellular Stress: A Therapeutic Perspective

“…One example would be β-catenin, which is highly mutated in liver, colon and prostate cancers, was previously reported to likely promote tumorigenesis through Wnt-dependent activity [20,21]. Alternatively, mutations in the cytoskeletal protein-related coding regions (CPCRs) within the genome and cytoskeletal-related proteins have been reported in several cancers, such as breast, melanoma and ovarian cancers [22][23][24]. These mutations could contribute to altered cytoskeletal activity during carcinogenesis.…”