CAF-derived OPN suppressed HCC cells’ sensitivity to tyrosine kinase inhibitors like sorafenib and lenvatinib by binding to adjacent HCC cells, activating a myriad of prosurvival and EMT pathways like RAF, MAPK, PI3K, AKT, mTOR, and PKCα (137). This evidence concerns the gene AKT1 and hepatocellular carcinoma.