Involvement of Actin and Actin-Binding Proteins in Carcinogenesis.

Magdalena Izdebska,Wioletta Zielińska,Alina Grzanka,Marta Hałas-Wiśniewska

doi:10.3390/cells9102245

Magdalena Izdebska, Wioletta Zielińska + Show 2 more

Open Access

https://doi.org/10.3390/cells9102245

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Abstract

The actin cytoskeleton plays a crucial role in many cellular processes while its reorganization is important in maintaining cell homeostasis. However, in the case of cancer cells, actin and ABPs (actin-binding proteins) are involved in all stages of carcinogenesis. Literature has reported that ABPs such as SATB1 (special AT-rich binding protein 1), WASP (Wiskott-Aldrich syndrome protein), nesprin, and villin take part in the initial step of carcinogenesis by regulating oncogene expression. Additionally, changes in actin localization promote cell proliferation by inhibiting apoptosis (SATB1). In turn, migration and invasion of cancer cells are based on the formation of actin-rich protrusions (Arp2/3 complex, filamin A, fascin, α-actinin, and cofilin). Importantly, more and more scientists suggest that microfilaments together with the associated proteins mediate tumor vascularization. Hence, the presented article aims to summarize literature reports in the context of the potential role of actin and ABPs in all steps of carcinogenesis.

Highlights

The cytoskeleton participates in many physiological processes
We focus on the participation of actin and ABPs in carcinogenesis and their influence on cancer progression and tumor vascularization
Altered levels of ABPs such as α-actinin, villin, filamin, formin, CFL1, Arp2/3, GLS, TAGLN, or fascin were found in many types of cancers, which correlated with poor clinical outcome [25,29,43,56,57,58,59,60,61]

Summary

Introduction

The cytoskeleton participates in many physiological processes. It is responsible for cell movement, division, differentiation, senescence, and death. The severing and capping proteins that target the actin filaments and regulate their length include CFL, villin, formin, and proteins of the GLS family. In the presence of calcium ions, GLS severs the actin filaments leading to the formation of caps at their barbed ends This is due to the sensitivity of segments 4–6 to calcium ions, whose binding causes a structural change in the protein. Wang et al suggest the proapoptotic and antiapoptotic impact of villin in small intestine epithelial cells [37] Another protein, Mena/VASP (mammalian enabled/vasodilator-stimulated phosphoprotein) is important during nucleation and polymerization of actin. Mena/VASP (mammalian enabled/vasodilator-stimulated phosphoprotein) is important during nucleation and polymerization of actin It is involved in the organization of the actin network in invasive protrusions and cell migration [38]. Altered levels of ABPs such as α-actinin, villin, filamin, formin, CFL1, Arp2/3, GLS, TAGLN, or fascin were found in many types of cancers, which correlated with poor clinical outcome [25,29,43,56,57,58,59,60,61]

Actin and ABPs in Carcinogenesis

Role of Actin in Angiogenesis and Vasculogenic Mimicry

Findings

Conclusions and Future Perspectives