Abstract

It is well established that mast cell accumulation accompanies most malignancies. However, the knowledge of how mast cells functionally impact on tumors is still rudimentary. Here we addressed this issue and show that mast cells have anti-proliferative activity on melanoma cells and that this effect is dependent on tryptase, a tetrameric protease stored in mast cell granules. Mechanistically, tryptase was found to be endocytosed by melanoma cells as cargo of DNA-coated exosomes released from melanoma cells, followed by transport to the nucleus. In the nucleus, tryptase executed clipping of histone 3 and degradation of Lamin B1, accompanied by extensive nuclear remodeling. Moreover, tryptase degraded hnRNP A2/B1, a protein involved in mRNA stabilization and interaction with non-coding RNAs. This was followed by downregulated expression of the oncogene EGR1 and of multiple non-coding RNAs, including oncogenic species. Altogether, these findings establish a new principle for regulation of tumor cell proliferation.

Published in

Cell death and disease
2019, Volume: 10, article number: 659
Publisher: NATURE PUBLISHING GROUP

SLU Authors

• Pejler, Gunnar

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Uppsala University

Sustainable Development Goals

SDG3 Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Cell Biology


Publication identifier

DOI: https://doi.org/10.1038/s41419-019-1879-4

Permanent link to this page (URI)

https://res.slu.se/id/publ/102191