Fig. 6

Schematic representation of the proposed model. P-cadherin-overexpressing cells significantly alter their biomechanical properties, presenting a decreased cellular height, cell stiffness and cell-cell adhesion strength. The activation of a mechanotransduction signaling initiated by P-cadherin overexpression, promotes an activation of SRC, with a concomitant delocalization of p120ctn to the cytoplasm, disrupting the E-cadherin/p120ctn complex, and activating the Rac1 small GTPase. Consistently, P-cadherin-overexpressing cells show a significantly higher number of protrusions, as well as increased protrusion’s length, increased cell migration, invasion, protease activity and self-renew potential. Molecularly, the expression of this basal marker affects: 1) cell-cell adhesion, through inhibition of the E-cadherin suppressive invasive function; 2) cell-ECM interaction, activating the heterodimer α6β4 integrin and 3) cell-ECM crosstalk, by regulating the activity of MMP1/MMP2 metalloproteases. Interestingly, inhibiting P-cadherin downstream SRC activation, using the FDA approved drug dasatinib, lead to a significant decrease in both morphological, biomechanical and functional properties induced by P-cadherin expression. In conclusion, the results anticipate an important role for P-cadherin in the mechanotransduction signaling in BCCs, which could be further inhibited by dasatinib