Transition of cancer cells across a continuum of states in response to therapy is emerging as a potential mechanism to develop drug tolerance23,85–87 and our data suggests that exposure of cells to stress could induce transition of some mesenchymal-low subpopulations into mesenchymal-high subpopulations, with SMAD3-KLF4-PPARG inducing the phenotypic switching. This evidence concerns the gene SMAD3 and cancer.