The cytoskeleton is a complex network of highly ordered intracellular ilaments that plays a central role in controlling cell shape, division, functions, and interactions in human organs and tissues, but dysregulation of this network can contribute to numerous human diseases, including cancer. To clarify the various functions of the cytoskeleton and its role in cancer progression, in this chapter, we will discuss the microilament (actin cytoskeleton), microtubule (β-tubulin), and intermediate ilament (keratins, cytokeratins, vimentin, and lamins) cytoskeletal structures; analyze the physiological functions of the cytoskeleton and its regulation of cell diferentiation; and investigate the roles of the cytoskeleton in cancer progression, the epithelial-mesenchymal transition process (EMT), and the mechanisms of multidrug resistance (MDR) in relation to the cytoskeleton. Importantly, the cytoskeleton, as a key regulator of the transcription and expression of many genes, is known to be involved in various physiological and pathological processes, which makes the cytoskeleton a novel and highly efective target for assessing the response to antitumor therapy in cancer.Keywords: Cytoskeleton, Regulator, cell diferentiation, drug resistance, EMT
IntroductionThe cytoskeleton is a structure similar to a bird's nest; it can be tightly packed or sparse and is found in both prokaryotes and eukaryotes [1]. The main component of the cytoskeleton is protein, and the speciic diferences in structure never afect the type of proteins incorporated [2]. The cytoskeletons of prokaryotes display apparent plasticity in composition, without conservation of the core ilament-forming proteins. However, the eukaryotic cytoskeleton has evolved in a variety of functions through the addition of accessory proteins and extensive There are three main cytoskeletal structures in eukaryotes, microilaments (MFs, ≈7 nm diameter), microtubules (MTs, ≈25 nm diameter), and intermediate ilaments (IFs, ≈10 nm diameter) [1]. MFs are responsible for cell contraction and reinforcement of the cell surface and allow changes in cell morphology. Actin and tubulin are the main globular proteins that form MFs and MTs, respectively. Actin is a ubiquitous eukaryotic ilament-forming protein. Actin ilaments (also called microilaments or F-actin) consist of two proto ilament polymers wound together in a right-handed helix [3]. Eukaryotic actin is a member of a large and diverse superfamily of ATPases that includes Hsp70 chaperones and several classes of sugar/sugar alcohol kinases [4,5] as well as eukaryotic actin-related proteins (ARPs) [6,7]. The actin cytoskeleton is involved in actin-based cytoskeletal structures, including various functionally distinct structures of actin organization, and can be regulated by actin regulatory proteins. It is well known that the actin cortex consists of a dense mesh-like array of F-actin anchored to the cell membranes [8,9]. This structure provides the core "skeleton" of the cell, functioning to deine cell shape and provi...