Using a mouse model of aggressive breast cancer due to the induced deficiency of Brca1 and p53 in the mammary luminal epithelium, we show that deletion of Itga6 in the tumor cells of origin, the luminal progenitors, impairs tumor formation through a mechanism involving: (i) inhibition of cell cycle progression associated to over-expression of p16 in pre-tumoral glands and (ii) interference with an EMT-like program normally occurring during the first stages of tumorigenesis triggered by Brca1/p53 loss. Here, ITGA6 is linked to breast carcinoma.