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Autocrine IL-1?-TRAF6 signalling promotes squamous cell carcinoma invasion through paracrine TNF? signalling to carcinoma-associated fibroblasts.


ABSTRACT: 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-1? signalling in SCC cells, which in turn is required to drive the expression of tumour necrosis factor ? (TNF?). TNF? acts in a paracrine manner to increase the invasion-promoting potential of carcinoma-associated fibroblasts (CAFs). Exogenous TNF? 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, TNF?, that enhances the activity of CAFs.

SUBMITTER: Chaudhry SI 

PROVIDER: S-EPMC3446864 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Autocrine IL-1β-TRAF6 signalling promotes squamous cell carcinoma invasion through paracrine TNFα signalling to carcinoma-associated fibroblasts.

Chaudhry S I SI   Hooper S S   Nye E E   Williamson P P   Harrington K K   Sahai E E  

Oncogene 20120326 6


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  ...[more]

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