IRS1 and hepatocellular carcinoma: On the other hand, in multiple myelomas, hepatocellular carcinoma, thyroid carcinoma and osteosarcomas, increased deptor expression suppresses mTORC1 activity, which increases the phosphorylation of Akt by relieving the negative feed-back loop on PI 3 kinase/IRS-1 [17, 66–68].