Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links

Abstract

Human tissues, to maintain their architecture and function, respond to injuries by activating intricate biochemical and physical mechanisms that regulates intercellular communication crucial in maintaining tissue homeostasis. Coordination of the communication occurs through the activity of different actin cytoskeletal regulators, physically connected to extracellular matrix through integrins, generating a platform of biochemical and biomechanical signaling that is deregulated in cancer. Among the major pathways, a controller of cellular functions is the cytokine transforming growth factor β (TGFβ), which remains a complex and central signaling network still to be interpreted and explained in cancer progression. Here, we discuss the link between actin dynamics and TGFβ signaling with the aim of exploring their aberrant interaction in cancer.

MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels

“…We have recently shown that MASTL regulates actin stress fiber formation and cell contractility in a kinase-independent manner by promoting MRTF-A/SRF-mediated transcription of actomyosin-related genes ( Taskinen et al., 2020 ). Dysregulation of cell contractility and TGF-β signaling is associated with cancer ( Melchionna et al., 2021 ). Interestingly, TGF-β has been shown to trigger nuclear translocation of MRTF-A and -B which coordinately regulate transcription of Slug, a well-known inducer of EMT with SMAD3 ( Morita et al., 2007 ).…”

Matrix Adhesiveness Regulates Myofibroblast Differentiation from Vocal Fold Fibroblasts in a Bio-orthogonally Cross-linked Hydrogel

“…With TGF-β1 treatment, the F-actin filamentous structures became longer and more extended. 44 Quantitative image analysis of the live/dead results revealed high percentages of viable cells (>89%) under all four conditions throughout the 14 days of culture (Figure 3C), confirming the cytocompatiblity of the bioorthogonal hydrogel platform.…”

Effects of β2 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis

“…When α and β subunit cytoplasmic tails bind to the salt bridge and ligands bind to the binding sites, the extracellular domain changes from a bent conformation to a highly extended conformation, thereby enhancing the binding affinity of integrins to ligands [ 31 , 32 ] ( Figure 2 ). Cells maintain dynamic cell–ECM contact by modulating cytoskeleton filaments and their connections with transmembrane proteins [ 33 ]. The cytoskeleton, a key cellular component, is composed of a system of filaments that includes microtubules, microfilaments, and intermediate filaments.…”