N-cadherin dependent collective cell invasion of prostate cancer cells is regulated by the N-terminus of α-catenin.
Cancer cell invasion is the critical first step of metastasis, yet, little is known about how cancer cells invade and initiate metastasis in a complex extracellular matrix. Using a cell line from bone metastasis of prostate cancer (PC3), we analyzed how prostate cancer cells migrate in a physiologically relevant 3D Matrigel. We found that PC3 cells migrated more efficiently as multi-cellular clusters than isolated single cells, suggesting that the presence of cell-cell adhesion improves 3D cell migration. Perturbation of N-cadherin function by transfection of either the N-cadherin cytoplasmic domain or shRNA specific to N-cadherin abolished collective cell migration. Interestingly, PC3 cells do not express α-catenin, an actin binding protein in the cadherin complex. When the full-length α-catenin was re-introduced, the phenotype of PC3 cells reverted back to a more epithelial phenotype with a decreased cell migration rate in 3D Matrigel. Interestingly, we found that the N-terminal half of α-catenin was sufficient to suppress invasive phenotype. Taken together, these data suggest that the formation of N-cadherin junctions promotes 3D cell migration of prostate cancer cells, and this is partly due to an aberrant regulation of the N-cadherin complex in the absence of α-catenin.
Department of Biomedical Engineering, University of California Davis, Davis, California, USA.
Yuanyuan
Y
Cui
Soichiro
S
Yamada
D015820:Cadherins / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051178:alpha Catenin / Q000378:metabolism / Q000502:physiology*
D015820:Cadherins; D051178:alpha Catenin