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IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-α dependent mechanism
Published in John Wiley and Sons Inc.
2015
PMID: 25358651
Volume: 54
   
Issue: 12
Pages: 1686 - 1699
Abstract
Fanconi anemia (FA) is a rare autosomal recessive genetic disorder associated with a bone-marrow failure, genome instability, hypersensitivity to DNA crosslinking agents and a predisposition to cancer. Mutations have been documented in 16 FA genes that participate in the FA-BRCA DNA repair pathway, a fundamental pathway in the development of the disease and the presentation of its symptoms. FA cells have been characterized by an overproduction of cytokines, MAPKs, and Interleukins. Through this study we have identified the overexpression of additional secretory factors such as IL-6, IL-8, MMP-2, and MMP-9 in FA cells and in cells depleted of FANCA or FANCC and proved that their expression is under the control of NF-κB/TNF-α signaling pathways. We also demonstrated that these overexpressed secretory factors were effective in promoting the proliferation, migration, and invasion of surrounding tumor cells a fundamental event in the process of epithelial mesenchymal transition (EMT) and that they also modulated the expression of EMT markers such as E-cadherin and SNAIL. Overall our data suggest that the upregulation of EMT promoting factors in FA may contribute to predisposing FA patients to cancer, thereby providing new insights into possible therapeutic interventions. © 2014 Wiley Periodicals, Inc.
About the journal
JournalData powered by TypesetMolecular Carcinogenesis
PublisherData powered by TypesetJohn Wiley and Sons Inc.
ISSN08991987
Open AccessNo
Concepts (59)
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    GELATINASE A
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    GELATINASE B
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    Immunoglobulin enhancer binding protein
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    Interleukin 6
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    INTERLEUKIN 8
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    TRANSCRIPTION FACTOR SNAIL
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    Tumor necrosis factor alpha
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    UVOMORULIN
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    Cadherin
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    FANCA PROTEIN, HUMAN
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    FANCC PROTEIN, HUMAN
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    FANCONI ANEMIA GROUP A PROTEIN
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    FANCONI ANEMIA GROUP C PROTEIN
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    GELATINASE A
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    GELATINASE B
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    IL6 PROTEIN, HUMAN
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    INTERLEUKIN 8
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    SNAIL FAMILY TRANSCRIPTION FACTORS
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    TNF PROTEIN, HUMAN
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    Transcription factor
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    Article
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    CANCER SUSCEPTIBILITY
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    Cell invasion
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    Cell migration
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    Cell proliferation
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    Controlled study
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    Epithelial mesenchymal transition
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    FANCONI ANEMIA
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    HIGH RISK POPULATION
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    Human
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    Human cell
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    Priority journal
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    Protein expression
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    Regulatory mechanism
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    Upregulation
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    Cell motion
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    FANCONI ANEMIA
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    Genetics
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    Mcf 7 cell line
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    Signal transduction
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    Tumor cell line
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    Tumor invasion
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    Cadherins
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    Cell line, tumor
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    Cell movement
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    Epithelial-mesenchymal transition
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    FANCONI ANEMIA
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    FANCONI ANEMIA COMPLEMENTATION GROUP A PROTEIN
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    FANCONI ANEMIA COMPLEMENTATION GROUP C PROTEIN
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    Humans
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    Interleukin-6
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    INTERLEUKIN-8
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    MATRIX METALLOPROTEINASE 2
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    MATRIX METALLOPROTEINASE 9
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    Mcf-7 cells
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    Neoplasm invasiveness
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    NF-KAPPA B
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    Transcription factors
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    Tumor necrosis factor-alpha