HA/CD44 interactions activate many signaling pathways of protein kinases, cytoskeletal changes, as well as intracellular pathways including Ras, MAPK, and phosphoinositide 3-kinases (PI3K) that contribute to cancer cell division, proliferation, invasion, and angiogenesis, as well as metabolic shift [197,198,202,218,219]. The gene discussed is CD44; the disease is cancer.