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

Oncogene volume 32, pages 747–758 (2013)Cite this article

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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-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.

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Acknowledgements

We thank the Cancer Research UK for funding. We thank St George's Thomas Tatum Head and the Neck Unit staff involved in tissue collection, Martin Gore for providing reagents, and lab members for their advice and discussions.

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Authors and Affiliations

  1. Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, London, UK

    S I Chaudhry, S Hooper & E Sahai

  2. Oral Medicine, UCL Eastman Dental Institute and UCLHT Eastman Dental Hospital, London, UK

    S I Chaudhry

  3. Experimental Histopathology Laboratory, Cancer Research UK London Research Institute, London, UK

    E Nye

  4. Thomas Tatum Head and Neck Unit, St George's Hospital, London, UK

    P Williamson

  5. Institute of Cancer Research, London, UK

    K Harrington

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Correspondence to E Sahai.

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Chaudhry, S., Hooper, S., Nye, E. et al. Autocrine IL-1β-TRAF6 signalling promotes squamous cell carcinoma invasion through paracrine TNFα signalling to carcinoma-associated fibroblasts. Oncogene 32, 747–758 (2013). https://doi.org/10.1038/onc.2012.91

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