Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment. Issue 4 (August 2015)

• Record Type: Journal Article
• Authors: Vlahopoulos, Spiros A.; Cen, Osman; Hengen, Nina; Agan, James; Moschovi, Maria; Critselis, Elena; Adamaki, Maria; Bacopoulou, Flora; Copland, John A.; Boldogh, Istvan; Karin, Michael; Chrousos, George P.
• Is Part Of: Cytokine & growth factor reviews. Volume 26:Issue 4(2015)
• Page Start: 389
• Page End: 403
• Publication Date: 2015-08
• Subjects: Immunity -- Inflammation -- Homeostasis -- Cancer -- Nuclear Factor kappa B; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2015.06.001
• Languages: English
• ISSNs: 1359-6101

Abstract

Highlights: During inflammation, cytokines induce a sequential activation of different cell types. Malignant cells can express gene cohorts from different stages of the inflammatory cascade. Dysregulation of NF-κB enables combining programs of stem cells with differentiated cells. The result is an aberrant interaction with the host tissue and the immune system. Disruption of essential mediators of homeostasis has far-ranging effects on the organism. Abstract: Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells.