16 May 2019
β-catenin, AHR, Akt, AP-1, Bcl-2, Cancer, Carcinogenesis, Cell transition, Chronic inflammation, CD44, Cx32, E1Q, E12/E47, EBV, ECM, Extracellular matrix, Epidemiology, Epigenetics, ERK, FADD, Fibrosis, FoxC1, Genomics, GSC, HATs, HGF, LINE-1, microRNA, MMPs, MMP-2, MMP-9, Mutation, NF-κB, OSCC, p107, p130, p300, Pathogenesis, PBX, PI3K, PPAR-γ, Precancerous niche, Proteomics, RB1, RB1CC1, RBL1, SIP1, SP1, Slug, Snail, Somatic mutation theory, SOX, Src, Syk, STAT3, TALE, TCF3, TGF-β1, TIMP-1, TNFR1, TRADD, Twist1, VEGF, ZEB1, ZEB2
The attempt to restore homeostasis, once disrupted, such that complex signaling, crosstalk between ubiquitous proteins, and a diverse range of pathways gone awry is near impossible, especially in the presence of an ongoing pathogenic stimuli with incessant inflammation. This persistent inflammation, when unresolved, induces fibrosis with consequent remodeling of the extracellular matrix (ECM) which leads to the formation of the precancerous niche (PCN), the tipping point in the transition of normal to cancerous cells. Thus, the sustained disruption of homeostasis when confronted with limited adaptation capabilities either of cells or of the surrounding matrix and faced with chronic stress in the tissue microenvironment results in an escape strategy which, if unsuccessful, causes cells, tissue, or the organism to become unable to recover over the long term. All conditions necessary for cell–cell transition such as deregulation of cell–cell complexes, decrease in the stability of adherens junctions, together with the apical-basal polarity, and the loss of the cytoskeletal architecture occurs as a cascade of events inducing inappropriate and diverse signaling pathways and crosstalk. In biology, the transition of one cell type to another and the transition from one cell function to another is incompletely understood mechanistically, but within the context of embryogenesis and morphogenesis is acknowledged as a physiologically routine event. The constant stress that can result in the development of the PCN leads to a chronic stress escape strategy (CSES) which, if unsuccessful, eventually triggers a normal cell- to-cancer cell- transition (NCCCT).