Abstract
Macrophage infiltration and inflammatory cytokines are powerful drivers of tumorigenesis and metastasis. Wu et al., in this issue of Cancer Cell, show that TNFalpha-dependent NFkappaB activation induces COP9 signalosome-mediated inhibition of GSK3beta and the SCF(beta-TRCP) ubiquitin ligase, thus leading to stabilization of the transcription factor Snail and promoting cell migration and metastasis.
MeSH terms
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Animals
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COP9 Signalosome Complex
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Cell Movement / physiology
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Cell Transformation, Neoplastic / metabolism*
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Glycogen Synthase Kinase 3 / antagonists & inhibitors
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Glycogen Synthase Kinase 3 beta
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Humans
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Inflammation / metabolism
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Macrophages / metabolism
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Macrophages / pathology
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Multiprotein Complexes / metabolism
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NF-kappa B / metabolism
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Neoplasm Metastasis*
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Peptide Hydrolases / metabolism
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SKP Cullin F-Box Protein Ligases / antagonists & inhibitors
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Signal Transduction
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Snail Family Transcription Factors
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Transcription Factors / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Multiprotein Complexes
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NF-kappa B
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Snail Family Transcription Factors
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Transcription Factors
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Tumor Necrosis Factor-alpha
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SKP Cullin F-Box Protein Ligases
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3
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Peptide Hydrolases
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COP9 Signalosome Complex