On the other hand, it was found that the ligand-dependent activation of RTKs, such as HER-1, insulin-like growth factor type 1 receptor (IGF-1R), or vascular endothelial growth factor receptor 1 (VEGFR-1), which are frequently overexpressed in cancers, induced MMP9 expression through PI3K/Akt- and MAPK/ERK1/2-dependent signals, such as the signal transducer and activator of transcriptions 3 and 5 (STAT3 and STAT5), and blocking of RTK–ligand interactions, and prevented MMP9 upregulation and inhibited MMP9-mediated cancer cell invasion [38,74,88,89,90]. Here, STAT3 is linked to cancer.