Myopodin isoforms alter the chemokinetic response of PC3 cells in response to different migration stimuli via differential effects on Rho-ROCK signaling pathways.
The gene encoding myopodin, an actin binding protein, is commonly deleted in invasive, but not in indolent, prostate cancers. There are conflicting reports on the effects of myopodin expression on prostate cancer cell migration and invasion. The recent recognition that myopodin is expressed as four different isoforms further complicates our understanding of how this potentially important invasive prostate cancer biomarker affects tumor cell migration and invasion. We now show that myopodin affects the chemokinetic, rather than the chemotactic, properties of PC3 prostate cancer cells. Furthermore, all myopodin isoforms can either increase or decrease PC3 cell migration in response to different chemokinetic stimuli. These migration properties were reflected by differences in cell morphology and the relative dependence on Rho-ROCK signaling pathways induced by the environmental stimuli. Truncation analysis determined that a unique 9-residue C-terminal sequence in the shortest isoform and the conserved, PDZ domain-containing N-terminal region of the long isoforms both contribute to the ability of myopodin to alter the response of PC3 cells to chemokinetic stimuli. Matrigel invasion assays also indicated that myopodin primarily affects the migration, rather than the invasion, properties of PC3 cells. The correlation between loss of myopodin expression and invasive prostate cancer therefore reflects complex myopodin interactions with pathways that regulate the cellular migration response to diverse signals that may be present in a tumor microenvironment.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 4R2.
FuiBoon
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Kai
Kaitlyn
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Tanner
Caroline
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Duncan
D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology*; D003001:Cloning, Molecular; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D024461:Myosin Type I / Q000378:metabolism; D025102:Myosin Type III / Q000378:metabolism; D041681:NIH 3T3 Cells; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
D018925:Chemokines; C062291:MYO1A protein, human; D008840:Microfilament Proteins; D020033:Protein Isoforms; C503979:SYNPO2 protein, human; C491724:MYO3A protein, human; D054460:rho-Associated Kinases; D024461:Myosin Type I; D025102:Myosin Type III; D018995:Myosin Heavy Chains; D020741:rho GTP-Binding Proteins