In turn, high molecular weight (>100 kDa) tumor-derived hyaluronan (HA) in the tumor microenvironment binds to CD44 and activates the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin complex 1 (mTORC2) signaling pathway. This evidence concerns the gene AKT1 and neoplasm.