Figure 8.

GSK3β ablation induces cell invasion via downregulation of CD82. (a and b) FaDu cells were infected with lentivirus expressing shRNA against GSK3β (sh3β-1) or a control (shC), and subsequently infected with recombinant retrovirus expressing either CD82 or a vector control (c). Puromycin-resistant cells were subjected to western blotting (a), or cell invasion assays (b), as described previously. Results from cell invasion assays were quantitated and presented as means and S.E. from three independent experiments. (c) A working model for ΔNp63α inhibition of cell invasion via CD82 and a role for GSK3β signaling. ΔNp63α upregulates CD82 expression, leading to the inhibition of cell invasion and cancer metastasis. GSK3β is important for ΔNp63α expression, either through an unidentified mechanism (as in the case of this study) or through the downregulation of Snail, which inhibits ΔNp63α expression via Snail-mediated suppression of C/EBP.⁴⁶ GSK3β also inhibits EMT by targeting Snail to proteasomal degradation, thereby suppressing cell invasion and cancer metastasis