In the current study, we used the mouse model of KRT5-Cre driven conditional knockout of TGF-β2 and N-butyl-N-4-hydroxybutyl Nitrosamine (BBN) induced BCa to demonstrate that ablation of TGF-β signaling could inhibit the progression, invasion and cancer stem cell population of BCa as well as the EMT. This evidence concerns the gene KRT5 and cancer.