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Author Notes:

Author for correspondence: Sue-Hwa Lin, slin@mdanderson.org.

S.-H.L., L.-Y.Y.-L., A.P.K. and R.L.S. conceived and designed the experiments.

T.P., M.A.B., X.L., Y.-C.L. and A.O. performed the experiments.

R.L.S., T.P., L.-Y.Y.-L. and S.-H.L. analyzed the data.

R.L.S., T.P., A.P.K., L.-Y.Y.-L. and S.-H.L. wrote the manuscript.

The authors declare no competing or financial interests.


Research Funding:

This work was supported by grants from the National Institutes of Health [grant numbers P50 CA140388 to S.H.L., CA174798 to S.H.L. and CA16672 to M.D. Anderson Cancer Center]; the Prostate Cancer Foundation to S.H.L.; Cancer Prevention and Research Institute of Texas [grant numbers CPRIT RP110327 to S.H.L., RP150179 to S.H.L. and RP150282 to S.H.L. and G.E.G.]; by funds from the Sister Institute Network Fund to S.H.L.; by the Institutional Start-up fund to R.L.S.; and by the Institutional Research Grant (IRG) Program at the MD Anderson Cancer Center to R.L.S.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • Cadherin-11
  • Clathrin
  • Endocytosis
  • Migration
  • Prostate cancer

Cadherin-11 endocytosis through binding to clathrin promotes cadherin-11-mediated migration in prostate cancer cells


Journal Title:

Journal of Cell Science


Volume 128, Number 24


, Pages 4629-4641

Type of Work:

Article | Final Publisher PDF


©2015.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 clathrinmediated internalization of Cad11 regulates surface trafficking of Cad11 and that dynamic turnover of Cad11 regulates the migratory function of Cad11 in prostate cancer cells.

Copyright information:

© 2015. Published by The Company of Biologists Ltd.

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