The goal of this study is to elucidate the genes and signaling pathways regulating oncogenic properties of cancer cells especially the survival and invasive abilities.For this purpose, we selected from low invasive human breast cancer lines MCF-7 and MDA-MB453 to derive respective highly invasive lines.Those pairs of lines were subjected to cDNA and miRNA array analysis, as well as comparison of various signaling pathways.We observed increased expression of Twist and AKT2, as well as activation of STAT3 in the invasive but not in the parental lines.Those molecules were further examined for signaling and functional linkage.Our results indicated that STAT3 bound to twist promoter and activated its transcription, Twist in turn bound to AKT2 promoter to activate its transcription.The STAT3-TwistAKT2 signaling axis plays an important role in regulating breast cancer cell anchorage independent growth,migration/invasion and resistance to paclitaxel.