The role of keratins in modulating carcinogenesis via communication with cells of the immune system

Cell Stress. 2019 Mar 23;3(4):136-138. doi: 10.15698/cst2019.04.184.


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.

Keywords: Krt76; anti-tumour; cancer; immunoregulation; keratin; regulatory T cells.

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