The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer

Figure 2

The role of COX-2/PGE₂ pathway in colitis-associated CRC. The COX enzymes catalyze the biosynthesis of PGG₂ and PGH₂ from arachidonic acid. PGH₂ is subsequently metabolized to TXA₂, PGI₂, PGE₂, PGD₂, and PGF_2α by PG synthases. COX-2-derived PGE₂ acts via specific receptor EP1-4 and plays an important role in tumor development and progression through inducing expression of antiapoptotic proteins (such as BCL-2), proangiogenic chemokines (such as CXCL1), and MMP. In addition, PGE₂ mediates the activation of PPARδ through PI3K/Akt signaling. PPARδ contributes to tumorigenesis by ensuring tumor cell survival and proliferation. Activation of PPARδ can further enhance the production of COX-2-derived PGE₂.