Inflammation-driven carcinogenesis in ulcerative colitis: Molecular and immunological pathways

Figure 1 Main signaling pathways and genes involved in the pathogenesis of ulcerative colitis and its progression to colitis-associated colorectal cancer. The inflammatory, immunological, and molecular mechanisms involved in epithelial barrier dysfunction, chronic intestinal inflammation, and neoplastic transformation are described. STAT3: Signal transducer and activator of transcription 3; NF-κβ: Nuclear factor kappa-light-chain-enhancer of activated B cells; IL-6: Interleukin-6; IL-11: Interleukin-11; SP1: Specificity protein 1; JAK: Janus kinase; TGFβ: Transforming growth factor beta; VEGF: Vascular endothelial growth factor; IKK: Complex an enzyme group made of subunits like Ikappa α, Ikappa β, and Ikappa γ; IKβ: Ikappa B kinase; COX-2: Cyclooxygenase-2; RTKs: Receptor tyrosine kinase; LPS: Lipopolysaccharide; TNF-α: Tumor necrosis factor alpha; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B; ZO-1: Zonula occludens-1; MAPK: Mitogen-activated protein kinase; UC-CRC: Ulcerative colitis associated colorectal cancer; KRAS: Kirsten rat sarcoma viral oncogene homolog; IDH15: Isocitrate dehydrogenase 15; APC: Adenomatous polyposis coli; PI3KCA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; IRS1: Insulin receptor substrate 1; PI3KR1: Phosphoinositide-3-kinase regulatory subunit 1; PDK1: Pyruvate dehydrogenase kinase 1; AKT1: Serine/threonine kinase 1; AKT2: Serine/threonine kinase 2; PAK4: P21-activated kinase 4; mTOR: Mammalian target of rapamycin; PTEN: Phosphatase and tensin homolog; TSC1/2: Tuberous sclerosis complex subunit 1/2; SOCS: Suppressor of cytokine signaling; PIAS: Protein Inhibitor of Activated STAT; PTPs: Protein tyrosine phosphatases; mTORC1: Mechanistic target of rapamycin complex 1; ULK: Unc-51-like kinase; ROS: Reactive oxygen species; NLRP3: Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3; AMPK: AMP-activated protein kinase.