Down-regulation of myopodin expression reduces invasion and motility of PC-3 prostate cancer cells.
Enhanced motility of cancer cells by remodelling of the actin cytoskeleton is crucial in the process of cancer cell invasion and metastasis. Although several studies propose a tumor suppressor role for the actin bundling protein myopodin, it was also shown previously that overexpression of mouse myopodin promotes invasion in vitro. In the present study, the role of myopodin in human cancer cell motility and invasion was explored using RNA interference with siRNA duplexes designed to down-regulate all human myopodin isoforms currently identified. We show that down-regulation of myopodin expression in human cancer cells significantly reduces the invasive properties of these cells both in collagen type I and in Matrigel. Furthermore, the motile characteristics of cancer cells are also curbed by reduced myopodin expression whereas cell-cell contacts are reinforced. These results point to a role for myopodin as tumor activator. While these findings are at variance with the suggested tumor suppressor role for myopodin, we hypothesize that the subcellular localization of the protein is involved in its suppressor or activator function in tumorigenesis.
Department of Medical Protein Research, VIB, B-9000 Ghent, Belgium.
Ariane
A
De Ganck
Veerle
V
De Corte
Erik
E
Bruyneel
Marc
M
Bracke
Joel
J
Vandekerckhove
Jan
J
Gettemans
D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014018:Tissue Distribution
D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C503979:SYNPO2 protein, human