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Whole exome sequencing of invasive mammary carcinomas revealed the association of mutations in <i>PTEN</i> and <i>ZFHX3</i> tumor suppressor genes (TSGs). We generated single and combined <i>PTEN</i> and <i>ZFHX3</i> knock-outs (KOs) in the immortalized mammary epithelial cell line MCF10A to study the role of these genes and their potential synergy in migration regulation. Inactivation of <i>PTEN</i>, but not <i>ZFHX3</i>, induced the formation of large colonies in soft agar. <i>ZFHX3</i> inactivation in <i>PTEN</i> KO, however, increased colony numbers and normalized their size. Cell migration was affected in different ways upon <i>PTEN</i> and <i>ZFHX3</i> KO. Inactivation of <i>PTEN</i> enhanced coordinated cell motility and thus, the collective migration of epithelial islets and wound healing. In contrast, <i>ZFHX3</i> knockout resulted in the acquisition of uncoordinated cell movement associated with the appearance of immature adhesive junctions (AJs) and the increased expression of the mesenchymal marker vimentin. Inactivation of the two TSGs thus induces different stages of partial epithelial-to-mesenchymal transitions (EMT). Upon double KO (DKO), cells displayed still another motile state, characterized by a decreased coordination in collective migration and high levels of vimentin but a restoration of mature linear AJs. This study illustrates the plasticity of migration modes of mammary cells transformed by a combination of cancer-associated genes.