Invadopodia formation, ECM degradation and the ensuing tumor spreading are finely regulated by specific signaling cascades that can share some elements, as is the case of Shp1 that, beside regulating invadopodia function, is a suppressor of TGF-β1-triggered EMT and of metastases through the dephosphorylation of STAT3 [26, 27]. Here, PTPN6 is linked to neoplasm.