ΔNp63α Promotes Breast Cancer Cell Motility through the Selective Activation of Components of the Epithelial-to-Mesenchymal Transition Program

摘要: Cell identity signals influence the invasive capability of tumor cells, as demonstrated by selection for programs epithelial-to-mesenchymal transition (EMT) during malignant progression. Breast cancer cells retain canonical epithelial traits and invade collectively cohesive groups but signaling pathways critical to their capabilities are still incompletely understood. Here we report that transcription factor ΔNp63α drives migration basal-like breast (BLBC) inducing a hybrid mesenchymal/epithelial state. Through combination expression analysis functional testing across multiple BLBC cell populations, determined induces elevating EMT program components Slug Axl. Interestingly, also increased miR-205, which can silence ZEB1/2 prevent loss character caused induction. In clinical specimens, co-expression various elements pathway confirmed its implication in motility BLBC. We observed activation occurred from noninvasive ductal carcinoma situ cancer. Notably, an orthotopic model, was sufficient induce collective invasion E-cadherin-expressing cells. Together, our results illustrate how drive selectively engaging promigratory while, parallel, promoting retention character.