Galectin-3 Overrides PTRF/Cavin-1 Reduction of PC3 Prostate Cancer Cell Migration.
Expression of Caveolin-1 (Cav1), a key component of cell surface caveolae, is elevated in prostate cancer (PCa) and associated with PCa metastasis and a poor prognosis for PCa patients. Polymerase I and Transcript Release Factor (PTRF)/cavin-1 is a cytoplasmic protein required for Cav1-dependent formation of caveolae. Expression of PTRF reduces the motility of PC3 cells, a metastatic prostate cancer cell line that endogenously expresses abundant Cav1 but no PTRF and no caveolae, suggesting a role for non-caveolar Cav1 domains, or Cav1 scaffolds, in PCa cell migration. Tyrosine phosphorylated Cav1 (pCav1) functions in concert with Galectin-3 (Gal3) and the galectin lattice to stabilize focal adhesion kinase (FAK) within focal adhesions (FAs) and promote cancer cell motility. However, whether PTRF regulation of Cav1 function in PCa cell migration is related to Gal3 expression and functionality has yet to be determined. Here we show that PTRF expression in PC3 cells reduces FAK stabilization in focal adhesions and reduces cell motility without affecting pCav1 levels. Exogenous Gal3 stabilized FAK in focal adhesions of PTRF-expressing cells and restored cell motility of PTRF-expressing PC3 cells to levels of PC3 cells in a dose-dependent manner, with an optimal concentration of 2 µg/ml. Exogenous Gal3 stabilized FAK in focal adhesions of Gal3 knockdown PC3 cells but not in Cav1 knockdown PC3 cells. Cav1 knockdown also prevented Gal3 rescue of FA-associated FAK stabilization in PTRF-expressing PC3 cells. Our data support a role for PTRF/cavin-1, through caveolae formation, as an attenuator of the non-caveolar functionality of Cav1 in Gal3-Cav1 signalling and regulation of focal adhesion dynamics and cancer cell migration.
Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Fanrui
F
Meng
Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Bharat
B
Joshi
Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Ivan Robert
IR
Nabi
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004795:Enzyme Stability / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000235:genetics; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
C497835:CAVIN1 protein, human; D037502:Galectin 3; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases