The remodelling of actin composition as a hallmark of cancer

Abstract

Actin is a key structural protein that makes up the cytoskeleton of cells, and plays a role in functions such as division, migration, and vesicle trafficking. It comprises six different cell-type specific isoforms: ACTA1, ACTA2, ACTB, ACTC1, ACTG1, and ACTG2. Abnormal actin isoform expression has been reported in many cancers, which led us to hypothesize that it may serve as an early biomarker of cancer. We show an overview of the different actin isoforms and highlight mechanisms by which they may contribute to tumorigenicity. Furthermore, we suggest how the aberrant expression of actin subunits can confer cells with greater proliferation ability, increased migratory capability, and chemoresistance through incorporation into the normal cellular F-actin network and altered actin binding protein interaction. Studying this fundamental change that takes place within cancer cells can further our understanding of neoplastic transformation in multiple tissue types, which can ultimately aid in the early-detection, diagnosis and treatment of cancer.

Keywords: Actin; Cancer; Cytoskeleton; Migration; Neoplasia; Transformation.

Graphical abstract

Fig. 1

A schematic representation of the different actin isoforms. Top panel - karyotype marking of the particular chromosome with the locus of each actin gene marked in red. Bottom panel – actin fibre schematic with regions of variability at the N-terminus of each actin isoform. Regions of the same colour represent an identical amino acid sequence .

Fig. 2

Illustration of actin polymerization and steady-state treadmilling. ATP-actin subunits becomes added to the “+” or barbed end whereas the ADP-actin monomers dissociate from the “-” end of the F-actin filament.

Fig. 3

A flow diagram of the different actin isoforms and how they contribute to tumorigenicity. ACTA1 = α_skeletal-actin 1, ACTA2 = α_smooth-actin 2, ACTB = β_cyto-actin, ACTC1 = α_cardiac-actin 1, ACTG1 = γ_cyto-actin 1 and ACTG2 = γ_smooth-actin 2.

Fig. 4

Flow diagram of the potential mechanisms by which altered F-actin composition can promote tumorigenicity. .