Document Detail


Autocrine IL-1β-TRAF6 signalling promotes squamous cell carcinoma invasion through paracrine TNFα signalling to carcinoma-associated fibroblasts.
MedLine Citation:
PMID:  22450746     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The invasion of squamous cell carcinoma (SCC) is a significant cause of morbidity and mortality. Here, we identify an E3 ligase, Traf6 and a de-ubiquitinating enzyme, Cezanne/ZA20D1, as important regulators of this process in organotypic models. Traf6 can promote the formation of Cdc42-dependent F-actin microspikes. Furthermore, Traf6 has a key role in autocrine interleukin-1β signalling in SCC cells, which in turn is required to drive the expression of tumour necrosis factor α (TNFα). TNFα acts in a paracrine manner to increase the invasion-promoting potential of carcinoma-associated fibroblasts (CAFs). Exogenous TNFα signalling can restore invasion in cells depleted of Traf6. In conclusion, Traf6 has two important roles in SCC invasion: it promotes cell intrinsic Cdc42-dependent regulation of the actin cytoskeleton and enables production of the paracrine signal, TNFα, that enhances the activity of CAFs.
Authors:
S I Chaudhry; S Hooper; E Nye; P Williamson; K Harrington; E Sahai
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Publication Detail:
Type:  Journal Article     Date:  2012-03-26
Journal Detail:
Title:  Oncogene     Volume:  32     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-07     Completed Date:  2013-04-12     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  747-58     Citation Subset:  IM    
Affiliation:
Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Autocrine Communication
Carcinoma, Squamous Cell / metabolism*
Endopeptidases / metabolism*
Fibroblasts / metabolism*
Humans
Interleukin-1beta / metabolism
Neoplasm Invasiveness
Paracrine Communication
Signal Transduction
TNF Receptor-Associated Factor 6 / metabolism*
Tumor Necrosis Factor-alpha / metabolism
cdc42 GTP-Binding Protein / metabolism
Chemical
Reg. No./Substance:
0/Interleukin-1beta; 0/TNF Receptor-Associated Factor 6; 0/Tumor Necrosis Factor-alpha; EC 3.4.-/Endopeptidases; EC 3.4.-/OTUD7B protein, human; EC 3.6.5.2/cdc42 GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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