Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment

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.

Androgen receptor (AR) signaling promotes RCC progression via increased endothelial cell proliferation and recruitment by modulating AKT → NF-κB → CXCL5 signaling

“…In addition, inflammation is also highly related to tumor angiogenesis40. NF-κB, the key player in inflammation, may also be involved in recruiting inflammatory immune cells to various tumors41 via PI3K/AKT signaling42. Indeed, we identified PI3K/Akt signaling as a downstream target of AR, which also led to increased CXCL5 expression through P65 translocation.…”

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

“…These signaling pathways activate various transcription factors including nuclear factor-κB (NF-κB). The later has the capacity to alter cell proliferation, differentiation, modulate state of the host tissue and of multiple components of the immune system (Brasier, 2006; Vlahopoulos et al, 2015). …”

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

“…When proteasome activity is impaired, its substrates may be imported into mitochondria to be degraded by mitophagy. 146,147 The degree of redundancy of these proteolytic systems in IjBa degradation depends on the cell type and the phase of the inflammatory cascade. 138 After the degradation of IjBa, NF-jB is translocated into the nucleus and interacts with nuclear hormone receptors, stress mediators, and tumor suppressors, to activate the expression of genes with different expression dynamics.…”

“…[219][220][221][222] Organelles, in turn, form intracellular networks that control autophagy and cell death. 147 CQ also impacts the dynamic interface between NF-jB, STAT3, p53, and GR, and the phenomena these proteins control, including mitochondrial membrane potential 229 and mitophagy. Their interactions impact the progress of the cell cycle, the response to nutritional changes, the induction of cell stress, organelle function, recycling and expression of cell surface molecules, and the secretion of diverse chemo-attractants.…”