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

Vlahopoulos, Spiros; Çen, Osman; Hengen, N.; Agan, James; Moschovi, Maria; Critselis, Elena; Adamaki, Maria; Bacopoulou, Flora; Copland, John A.; Boldogh, István; Karin, Michael; Chrousos, George P.

doi:10.1016/j.cytogfr.2015.06.001

Cited by 88 publications

(87 citation statements)

References 144 publications

(235 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 83%

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

Guan

Fan

et al. 2016

Sci Rep

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Androgen receptor (AR) signaling may promote renal cell carcinoma (RCC) progression via altered HIF-2α/VEGF signaling. However, it remains unclear whether AR signaling also promotes RCC progression by recruiting vascular endothelial cells (ECs), key players in the development of blood vessels. In our study, AR increased EC proliferation and recruitment to the tumor microenvironment and promoted RCC progression. Mechanistically, AR modulated cytokine CXCL5 expression by altering AKT → NF-κB signaling, and interruption of AKT → NF-κB → CXCL5 signaling using either specific inhibitors or siRNA suppressed AR-enhanced EC recruitment and AR-EC-promoted RCC progression. The results obtained using an in vivo mouse model and a human clinical sample survey confirmed the role of AR in promoting RCC progression through enhancement of EC proliferation and/or recruitment via altered AKT → NF-κB → CXCL5 signaling. Targeting this newly identified AR-induced AKT → NF-κB → CXCL5 pathway may facilitate the development of new therapies for slowing RCC progression.

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Section: Discussionmentioning

confidence: 83%

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

Guan

Fan

et al. 2016

Sci Rep

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“…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). …”

Section: Introductionmentioning

confidence: 99%

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

Germán

Saenz

Szaniszlo

et al. 2017

Mechanisms of Ageing and Development

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Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER “wires” senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed --86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

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“…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.…”

Section: Proteostasis Regulates Cellular Stress Responsesmentioning

confidence: 99%

“…[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.…”

Section: Cq Effects On Cancer Stem Cellsmentioning

confidence: 99%

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

2019

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Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.

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

Cited by 88 publications

References 144 publications

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

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

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

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

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