The role of keratins in modulating carcinogenesis via communication with cells of the immune system
Authors:Inês Sequeira1 and Fiona M. Watt1
1 Centre for Stem Cells & Regenerative Medicine, King’s College London, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK.
Keywords:
cancer, keratin, Krt76, regulatory T cells, immunoregulation, anti-tumour.
Corresponding Author(s):
Conflict of interest statement:
FMW is currently on secondment as Executive Chair of the UK Medical Research Council. The authors declare no other competing interests.
Please cite this article as:
FMW is currently on secondment as Executive Chair of the UK Medical Research Council. The authors declare no other competing interests.
© 2019 Sequeira and Watt. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.
Abstract:
Keratins are intermediate filament proteins expressed by epithelial cells and provide mechanical support for diverse epithelia. In our recent study (Sequeira et al., Nat Comm 9(1):3437), we analysed the role of keratin 76 (Krt76) in inflammation and cancer. Krt76 is expressed throughout embryonic development in the differentiated epithelial layers of a subset of stratified epithelia including tongue, palate and stomach. It is significantly downregulated in human oral squamous cell carcinoma (OSCC), correlating strongly with poor prognosis. We have shown that Krt76-/- mice exhibit systemic inflammation with increased levels of circulating B cells, regulatory T cells and effector T cells. When mice are given a chemical carcinogen in the drinking water, tongue and gastric cancer formation is accelerated in Krt76-/- mutant mice. Our data suggest that the increased tumour susceptibility of Krt76-/- mice is in part due to the enhanced accumulation of regulatory T cells in the tumour microenvironment. Our results support the notion that keratins, in addition to their function as cytoskeletal components, regulate immunity and affect tumour susceptibility of epithelial cells.