Tumor promotion by γ and suppression by β non-muscle actin isoforms.

Vera Dugina,Pavel Kopnin,Vera Rybko,Galina Shagieva,Natalya Khromova,Christine Chaponnier,Oleg Blizniukov,Boris Kopnin

doi:10.18632/oncotarget.3989

Abstract

Here we have shown that β-cytoplasmic actin acts as a tumor suppressor, inhibiting cell growth and invasion in vitro and tumor growth in vivo. In contrast, γ-cytoplasmic actin increases the oncogenic potential via ERK1/2, p34-Arc, WAVE2, cofilin1, PP1 and other regulatory proteins. There is a positive feedback loop between γ-actin expression and ERK1/2 activation. We conclude that non-muscle actin isoforms should not be considered as merely housekeeping proteins and the β/γ-actins ratio can be used as an oncogenic marker at least for lung and colon carcinomas. Agents that increase β- and/or decrease γ-actin expression may be useful for anticancer therapy.

Highlights

At the moment six highly conserved actin isoforms in vertebrates are known: four muscle and two nonmuscle
The main actin isoform studied in the context of carcinogenesis is the α-smooth muscle actin (ACTA2), which is expressed in normal smooth muscle cells, in myoepithelial cells and in myofibroblasts including tumorassociated fibroblasts [1]
We have studied the distribution of β- and γ-actins in normal cells compared with malignant human lung and colon epithelial cells

Summary

Introduction

At the moment six highly conserved actin isoforms in vertebrates are known: four muscle and two nonmuscle. The proportion of β- and γ-actins depends on the cell type [2, 5,6,7] Their expression differs in various tissues, depending on differentiation, but on functional activity of the cell. Nonmuscle actin isoforms play crucial roles in cell migration, division and even intracellular signaling [9]. The purpose of this study was to explore the roles of non-muscle cytoplasmiс β- and γ-actin isoforms expression changes in cell transformation and tumor progression. These proteins differ only in four amino acids near the N-terminus [2] and are expressed in normal epithelial cells. We have shown that β-actin is connected with contraction and adhesion, whereas γ-actin predominantly forms the cortical network necessary for shape flexibility and motile activity of normal fibroblasts and epithelial cells [10]

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