Inflammatory pathways in the early steps of colorectal cancer development

Table 1 Main players in inflammatory pathways related to early phases of colorectal cancer development

Player	Role in early steps of colorectal cancer
IL-23	Induction of IL-17, activation of PMN respiratory burst
IL-17	Production of inflammatory cytokines, neutrophils recruitment and activation
Arginase	Stimulation of cell growth, collagen deposition, and tissue repair
sialyl Lewis-A and sialyl Lewis-X	Their accumulation on neoplastic cell escape the binding with siglec-7 and -9 in macrophages, thus enhancing COX-2 production
MPO	Hypochlorous acid (HOCl) formation, promotion of neutrophil survival
MMP-8, MMP-9	Tissue destruction and remodeling
5-LOX	Induced by IL-4 and IL-13, role in first step of leukotriene synthesis. Generally absent in normal epithelia
LTB4, LTC4, LTD4, LTE4	Chemoattraction of PMN, eosinophils, and macrophages. Activation of PMN. Increased microvascular permeability. Proliferation of colon cancer cells
COX-2	PGE production, neutrophil accumulation, perpetuate of inflammatory responses, Wnt signalling activation
12-LOX	Cancer cell proliferation, metastasis, and angiogenesis. Generally absent in normal epithelia
15-LOX	Resolution of inflammation. Generally absent in cancer cells
Lipoxins, resolvins and protectins	Resolution of inflammation (stop of PMN recruitment and superoxide generation and release, stimulation of non-phlogistic monocyte infiltration, promotion of the uptake and clearance of apoptotic cells, increase the exit of phagocytes from the inflamed site)
ACSL4	Increased COX-2 and LOX-5 levels, controls of COX-2 and LOX-5 metabolism of AA, inhibition of apoptosis and increased cell proliferation
TFAM	Regulation of mtDNA transcription, replication and repair. Essential for mitochondrial biogenesis and function
HIF-1	Activate also by ROS, mediates adaptation to hypoxia. Regulation of cell survival, inhibition of apoptosis, neoangiogenesis and tumor metastasis
Nrf2	Antioxidant enzymes expression, , promotion of cells survival by escaping to stress, cells proliferation, and metastasis
SIRT1	Regulation of both apoptosis and autophagy
SIRT3	Regulation of ROS homeostasis
IL-22	Promotion of epithelial repair
NF-κB	Activated by TNF-α, IL-1 and ROS, regulation of infection and inflammation. Apoptosis inhibition. Regulation of cyclin D1, cMyc, VEGF and IL-8

IL: Interleukin; MPO: Myeloperoxidase; MMPs: Matrix metalloproteinases; LOX: Lipoxygenase; ACSL4: Acyl-CoA synthetase 4; TFAM: Mitochondrial transcription factor A; HIF1: Hypoxia inducible factor 1; Nrf2: Nuclear factor erythroid 2-related factor 2; SIRT1–7: Seven sirtuins; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; PMN: Polymorphonuclear cells; TNF-α: Tumor necrosis factor α; VEGF: Vascular endothelial growth factor.