title: Cadherin-11 endocytosis through binding to clathrin promotes cadherin-11-mediated migration in prostate cancer cells.
abstract: Cadherin-11 (Cad11) cell adhesion molecule plays a role in prostate cancer cell migration. Because disassembly of adhesion complexes through endocytosis of adhesion proteins has been shown to play a role in cell migration, we examined whether Cad11 endocytosis plays a role in Cad11-mediated migration. The mechanism by which Cad11 is internalized is unknown. Using a GST pulldown assay, we found that clathrin binds to the Cad11 cytoplasmic domain but not to that of E-cadherin. Using deletion analysis, we identified a unique sequence motif, VFEEE, in the Cad11 membrane proximal region (amino acid residues 11-15) that binds to clathrin. Endocytosis assays using K(+)-depletion buffer showed that Cad11 internalization is clathrin dependent. Proximity ligation assays showed that Cad11 colocalizes with clathrin, and immunofluorescence assays showed that Cad11 localizes in vesicles that stain for the early endosomal marker Rab5. Deletion of the VFEEE sequence from the Cad11 cytoplasmic domain (Cad11-cla-Δ5) leads to inhibition of Cad11 internalization and reduces Cad11-mediated cell migration in C4-2B and PC3-mm2 prostate cancer cells. These observations suggest that clathrin-mediated internalization of Cad11 regulates surface trafficking of Cad11 and that dynamic turnover of Cad11 regulates the migratory function of Cad11 in prostate cancer cells.
authors.affiliation: Department of Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Satcher
authors.affiliation: Department of Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Pan
authors.affiliation: Department of Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Mehmet A
authors.initials: MA
authors.lastname: Bilen
authors.affiliation: Department of Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Angelica
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Kowalczyk
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Yu-Lee
authors.affiliation: Department of Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA Department of Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA slin@mdanderson.org.
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding
chemical_list: D015820:Cadherins; D002966:Clathrin; D009363:Neoplasm Proteins; C086960:osteoblast cadherin
keywords: Cadherin-11; Clathrin; Endocytosis; Migration; Prostate cancer