Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells

We demonstrate that in REF52 fibroblasts, decreased levels of SM22 disrupt normal actin organization leading to changes in the motile behaviour of cells. Interestingly, SM22 depletion also led to an increase in the capacity of cells to spontaneously form podosomes with a concomitant increase in the ability to invade Matrigel. In PC3 prostate epithelial cancer cells by contrast, where SM22 is undetectable, re-expression of SM22 reduced the ability to invade Matrigel. Furthermore SM22 depleted cells also had reduced levels of reactive oxygen species when under serum starvation stress.These findings suggest that depletion of SM22 could contribute to tumourigenic properties of cells. Reduction in SM22 levels would tend to promote cell survival when cells are under stress, such as in a hypoxic tumour environment, and may also contribute to increases in actin dynamics that favour metastatic potential.Smooth muscle protein of 22kDa (SM22α) was one of three protein isoforms (α,β,γ) first purified from chicken gizzard muscle but with no known function [1]. Several years later SM22 was rediscovered and named transgelin due to its apparent ability to induce gelation of actin filaments in vitro [2] however subsequent analysis revealed that SM22 and transgelin were one and the same protein [3,4]. These and subsequent analyses have identified a family of related proteins variously known as mp20, NP22, NP25, p27, SM22α, SM22β, transgelin and WS3-10 (see [5] for brief review). Following the sequencing of various vertebrate genomes, it is now recognized that all these proteins arise from just three genes named TAGLN1-3, with SM22α, transgelin and WS3-10 being independently discovered, but identical products of the TAGLN1 gene, SM22β the product of TAGLN2 and the neuronally expressed NP22 and NP25 the product of TAGLN3. SM22 is a member of the calponin family of proteins [6] all of which comprise an amino-terminal calponin homology (CH) domain and from one (SM22) to three (calponin)