Alterations of Cytoskeleton Networks in Cell Fate Determination and Cancer Development

Abstract

Cytoskeleton proteins have been long recognized as structural proteins that provide the necessary mechanical architecture for cell development and tissue homeostasis. With the completion of the cancer genome project, scientists were surprised to learn that huge numbers of mutated genes are annotated as cytoskeletal or associated proteins. Although most of these mutations are considered as passenger mutations during cancer development and evolution, some genes show high mutation rates that can even determine clinical outcomes. In addition, (phospho)proteomics study confirms that many cytoskeleton-associated proteins, e.g., β-catenin, PIK3CA, and MB21D2, are important signaling mediators, further suggesting their biofunctional roles in cancer development. With emerging evidence to indicate the involvement of mechanotransduction in stemness formation and cell differentiation, mutations in these key cytoskeleton components may change the physical/mechanical properties of the cells and determine the cell fate during cancer development. In particular, tumor microenvironment remodeling triggered by such alterations has been known to play important roles in autophagy, metabolism, cancer dormancy, and immune evasion. In this review paper, we will highlight the current understanding of how aberrant cytoskeleton networks affect cancer behaviors and cellular functions through mechanotransduction.

Chorein sensitive microtubule organization in tumor cells

“…In contrast, alterations of cytoskeleton organization and signaling, as depicted formerly in various tumor cells ( Stournaras et al, 1996 ; Wang et al., 2022 ), appears to be a crucial dedifferentiation step ( Araki et al, 2015 ; Stournaras et al, 2014 ; Kotula, 2012 ; Papakonstanti & Stournaras, 2008 ). This interface may in turn govern key cellular functions of tumor cells.…”

Contribution of Autophagy to Epithelial Mesenchymal Transition Induction during Cancer Progression

“…Under these circumstances the cells can acquire the capacity to invade neighboring tissues and metastasize [8]. Consequently, cancer-associated modifications have the potential to perturb cellular fate decisions by impacting essential cellular processes such as proliferation, differentiation, metabolism, and cell death [9,10]. Exogenous and endogenous agents, including ionizing radiation, chemical carcinogens, oncoviruses, tobacco and alcohol consumption, as well as disorders that predispose individuals to DNA damage and cancer, are contributing factors [6,11].…”