SMAD2 and neoplasm: At the functional level, in tumor cells RHAMM‐HA interaction elicits multiple signaling cascades that regulate the following tumor‐related features: (a) it enhances cell motility and invasion, mainly by activating protein kinase C (PKC) [89, 90, 91]; (b) it boosts cell proliferation via regulating the expression of mitogen‐activated protein kinase (MAPK) [85], and (c) it induces epithelial‐to‐mesenchymal transition and multidrug resistance by increasing TGFβ/smad2 expression [92].