Autocrine IL-1 beta-TRAF6 signalling promotes squamous cell carcinoma invasion through paracrine INF alpha, signalling to carcinoma-associated fibroblasts

作者：Chaudhry S I; Hooper S; Nye E; Williamson P; Harrington K; Sahai E^*

来源：Oncogene, 2013, 32(6): 747-758.

DOI：10.1038/onc.2012.91

• Traf6
• Interleukin-1
• TNR alpha
• invasion
• carcinoma-associated fibroblast

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 beta signalling in SCC cells, which in turn is required to drive the expression of tumour necrosis factor alpha (TNF alpha). TNF alpha acts in a paracrine manner to increase the invasion-promoting potential of carcinoma-associated fibroblasts (CAFs). Exogenous TNF alpha 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 alpha, that enhances the activity of CAFs. Oncogene (2013) 32, 747-758; doi:10.1038/onc.2012.91; published online 26 March 2012

• 出版日期2013-2-7