This work reveals, for the first time, that p17 suppresses the formation of invadopodia in B16-F10 cancer cells by activation of the p53/PTEN pathway, inhibition of the FAK/Src pathway, and enhancement of the formation of the TKs5/ non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1) complex. This evidence concerns the gene SH3PXD2A and cancer.