Skip to main content
. Author manuscript; available in PMC: 2016 Apr 22.
Published in final edited form as: Cancer Res Front. 2016 Jan 21;2(1):1–21. doi: 10.17980/2016.1

Figure 2. Colonic epithelial inducible signaling in CAC development.

Figure 2

TLRs and NLRs bind with microbe associated molecular patterns (MAMP) or microbial products. In particular, binding of LPS with TLR4 results in NF-kB signaling and induces IL-6 and other pro-inflammatory cytokine production. IL6-IL-6R interaction exerts uncontrolled STAT3 mediated cell proliferation and tumor. Signaling through different NLRs converts pro IL-1β and IL-18 into biologically active IL-1β and IL-18 either through forming inflammasome complex or independent signaling. NLRs have been shown to suppress CAC development. However, IL-18 has been reported to play a dual role in CAC. CHI3L1, a secretory molecule, binds with multiple receptors including RAGE, IL-13Rα2 and syndecan-1/αVβ3, and induces carcinogenic and angiogenic signals, which promote CAC initiation and progression. Wnt-β-catenin signaling is crucial in cancer initiation, progression and metastasis. In addition, epithelial barrier significantly contributes to the pathogenesis of CAC through facilitating chronic inflammation. TNFR2-TNFα interaction upregulates MLCK which results in internalization of occludins and loss of epithelial barrier. Multiple signaling pathways are simultaneously induced in IECs upon chronic inflammation, which initiate the transition from dysplasia to CAC and favor successful progression.