In summary, our study indicates that the elevated stress protein TRIB3 links stress signals to induce breast cancer initiation and progression by supporting breast cancer stemness, which is coordinated with elevated FOXO1 and SOX2, and triggered by activation of the TRIB3-AKT1-FOXO1-SOX2 axis in TRIB3-overexpressed BCCs. Here, SOX2 is linked to breast cancer.