Loss of
E-cadherin-mediated cell-cell junctions has been correlated with
cancer cell invasion and poor patient survival.
p120-catenin has emerged as a key player in promoting
E-cadherin stability and adherens junction integrity and has been proposed as a potential invasion suppressor by preventing release of cells from the constraints imposed by
cadherin-mediated cell-cell adhesion. However, it has been proposed that
tyrosine phosphorylation of p120 may contribute to
cadherin-dependent junction disassembly during invasion. Here, we use
small interfering RNA (
siRNA) in A431 cells to show that knockdown of p120 promotes two-dimensional migration of cells. In contrast, p120 knockdown impairs
epidermal growth factor-induced A431 invasion into three-dimensional matrix
gels or in organotypic culture, whereas re-expression of
siRNA-resistant p120, or a p120
isoform that cannot be phosphorylated on
tyrosine, restores the collective mode of invasion employed by A431 cells in vitro. Thus, p120 promotes A431 cell invasion in a phosphorylation-independent manner. We show that the collective invasion of A431 cells depends on the presence of
cadherin-mediated (P- and
E-cadherin) cell-cell contacts, which are lost in cells where p120 expression is knocked down. Furthermore, membranous p120 is maintained in invasive
squamous cell carcinomas in tumours suggesting that p120 may be important for the collective invasion of tumours cells in vivo.