Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. This evidence concerns the gene TM4SF5 and neoplasm.