Mechanistically, at least in the BC cells, CCN5 issufficient to induce ER-α expression at the transcription level via interactingwith integrins-α6β1 and suppressing Akt followed by activation of FOXO3a.Moreover, in vitro and in vivo functional assays indicate that CCN5treatment promotes response to tamoxifen in triple-negative BC (TNBC) cells possiblyvia restoring ER-α. This evidence concerns the gene AKT1 and breast cancer.