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. 2022 Aug 25;29(9):6091–6114. doi: 10.3390/curroncol29090479

Figure 1.

Figure 1

The involvement of cytokine-related signaling pathways in colitis-associated CRC. (A) Binding of IL-23 to IL-23R activates the downstream JAK/STAT pathway to release IL-17A, IL-21, IL-22 from Th17 cells, exerting proinflammatory and protumor effects. (B–E) Several factors such as S1P, IL-22, IL-6, VEGF contribute to phosphorylation of STAT3 that upregulates Bcl-x and Caspase 3, downregulate Bcl-xl to inhibit apoptosis. (F) Kynurenine pathway metabolites rapidly activate PI3K/AKT signaling which then promotes β-catenin translocate to the nucleus, where β-catenin can form transcription complex with YAP and TCF4. (G–I) Proinflammatory stimuli including TNF-α, IL-1β and LPS can participate in tumor initiation and development through boosting the downstream molecule NF-κB activity. (J) PGE2 activates PI3K/AKT/PPAR-δ signaling to promote cell survival, thus increasing tumor burden.