Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer

Abstract

To date, substantial evidence has shown a significant association between inflammatory bowel diseases (IBD) and development of colitis-associated cancer (CAC). The incidence/prevalence of IBD is higher in western countries including the US, Australia, and the UK. Although CAC development is generally characterized by stepwise accumulation of genetic as well as epigenetic changes, precise mechanisms of how chronic inflammation leads to the development of CAC are largely unknown. Preceding intestinal inflammation is one of the major influential factors for CAC tumorigenesis. Mucosal immune responses including activation of aberrant signaling pathways both in innate and adaptive immune cells play a pivotal role in CAC. Tumor progression and metastasis are shaped by a tightly controlled tumor microenvironment which is orchestrated by several immune cells and stromal cells including macrophages, neutrophils, dendritic cells, myeloid derived suppressor cells, T cells, and myofibroblasts. In this article, we will discuss the contributing factors of epithelial as well as immune cell signaling in initiation of CAC tumorigenesis and mucosal immune regulatory factors in the colonic tumor microenvironment. In depth understanding of these factors is necessary to develop novel anti-inflammatory and anti-cancer therapies for CAC in the near future.

K284-6111 Alleviates Memory Impairment and Neuroinflammation in Tg2576 Mice by Inhibition of Chitinase-3-like 1 Regulating ERK Dependent PTX3 Pathway

“…Based on our in vivo and in vitro results, K284-6111 inhibits NF-κB and ERK signaling. [62]. In addition, we observed that p-IκBα was inhibited when the ERK inhibitor was treated, however, p-ERK was not changed when the NF-κB inhibitor was treated.…”

K284-6111 alleviates memory impairment and neuroinflammation in Tg2576 mice by inhibition of Chitinase-3-like 1 regulating ERK-dependent PTX3 pathway

“…He et al demonstrated that CHI3L1 binds to IL-13Rα2 and induces ERK, AKT, and Wnt/β-catenin signals independent of IL-13 pathway [ 63 ]. Subramaniam et al described in their review paper that CHI3L1 binds to RAGE (receptor for advance glycation end product), resulting in the activation of the NF-κB, β-catenin, and MAPK signaling pathways [ 64 ]. In addition, we observed that p-IκBα was inhibited when the ERK inhibitor was treated; however, p-ERK was not changed when the NF-κB inhibitor was treated.…”

K284-6111 prevents the amyloid beta-induced neuroinflammation and impairment of recognition memory through inhibition of NF-κB-mediated CHI3L1 expression

“…CHI3L1 has the ability to bind RAGE (receptor for advance glycation end product) which contributes to various cellular responses with enhanced activation of NF-κB, MAPK, and β-catenin signaling pathways [ 32 ]. NF-κB has been well documented in decreasing transcription factors regulating β-secretase in brain cells, resulting in neuronal cell death with accumulation of Aβs [ 11 ].…”