CCN5-mediated induction of ER-αexpression, at least in BC cells, is a transcriptional regulation through theintegrin α6β1-FOXO3a pathway and possibly via suppressing Akt-signaling.The involvement of same mechanism in regulation of CCN5-mediatedER-α-expression in normal mammary epithelial cells is also anticipated asFOXO3a ablation blocks CCN5-induced ER-α expression in HMEC cells. This evidence concerns the gene ESR1 and breast cancer.