Figure 7.

Schematic illustration of the proposed stimulation of HAS isoform regulation by prostaglandins in cancer cells. According to our working hypothesis COX2-dependent prostaglandins (PGI₂ and PGE₂) activate the Gα_s-coupled IP and EP_2/4 receptors, raise intracellular cAMP levels and in turn activate HAS1 and HAS2 expression via PKA-mediated signals. The increased HA secretion stimulates a malignant tumour cell phenotype through signalling via HA receptors CD44 or receptor of HA-mediated motility (RHAMM). The present findings indicate that in oesophageal squamous cancer cells, OSC1 and OSC2, stimulation of HAS1 and HAS2 expression by prostaglandins is inhibited either at the level of prostaglandin receptor-stimulated cAMP induction (OSC2) and/or downstream of cAMP (OSC1, OSC2).