Additionally, we found that specific knockdown of IRS1 expression or IRS1 gene deletion decreased the levels of p-Akt and p-FOXO3a in vivo (Supplementary Fig. 7c), confirming that p-Akt/p-FOXO3a acted as downstream of IRS1 in Herceptin-resistant breast cancer cells. Here, IRS1 is linked to breast carcinoma.