title: Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells.
abstract: BACKGROUND
  SM22 has long been studied as an actin-associated protein. Interestingly, levels of SM22 are often reduced in tumour cell lines, while they are increased during senescence possibly indicating a role for SM22 in cell fate decisions via its interaction with actin. In this study we aimed to determine whether reducing levels of SM22 could actively contribute to a tumourigenic phenotype.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Thompson
authors.forename: Jeelan S
authors.initials: JS
authors.lastname: Moghraby
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Ayscough
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Winder
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007797:Laminin; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D011509:Proteoglycans; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000199:Actins; D004338:Drug Combinations; D007797:Laminin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C051615:transgelin; C059485:matrigel; D003094:Collagen