Fig. 3

Schematic representation of Hyaluronic acid-mediated regulation of cell migration, invasion, differentiation and metastasis. 1) The interaction between HA and CD44 triggers the activation of ankyrin, leading to cytoskeleton rearrangement and facilitating cell adhesion. Ankyrin also plays a role in the release of calcium, which binds to the calmodulin II receptor. This binding event subsequently leads to the phosphorylation of filamin, promoting processes such as cell migration and invasion. 2) HA by binding with CD44 activates RhoA, which in turn, phosphorylates ROK (Rho-associated protein kinase) and initiates chain of events that contribute to cell growth, survival, and differentiation. These effects are achieved through the activation of myosin phosphatase, elevation of cellular acidity (lower pH), and enhancement of the PI3-AKT signaling pathway 3) HA and CD44 interaction induced the activation of Rac1, which subsequently promotes cell metastasis