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: Robert L Satcher, Tianhong Pan, Mehmet A Bilen, Xiaoxia Li, Yu-Chen Lee, Angelica Ortiz, Andrew P Kowalczyk, Li-Yuan Yu-Lee, Sue-Hwa Lin
• Journal: Journal of cell science (J Cell Sci) Vol. 128 Issue 24 Pg. 4629-41 (Dec 15 2015) ISSN: 1477-9137 [Electronic] England
• PMID: 26519476 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015. Published by The Company of Biologists Ltd.

Chemical References

• Cadherins
• Clathrin
• Neoplasm Proteins
• osteoblast cadherin

Topics

• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Clathrin (genetics, metabolism)
• Endocytosis
• HEK293 Cells
• Humans
• Male
• Neoplasm Proteins (genetics, immunology)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Protein Binding