Inhibition of the SRC Kinase HCK Impairs STAT3-Dependent Gastric Tumor Growth in Mice.

Cancer immunology research 2020 Apr

filter terms:

Persistent activation of the latent transcription factor STAT3 is observed in gastric tumor epithelial and immune cells and is associated with a poor patient prog nosis. Although targeting STAT3-activating upstream kinases offers therapeutically viable targets with limited specificity, direct inhibition of STAT3 remains challenging. Here we provide functional evidence that myeloid-specific hematopoietic cell kinase (HCK) activity can drive STAT3-dependent epithelial tumor growth in mice and is associated with alternative macrophage activation alongside matrix remodeling and tumor cell invasion. Accordingly, genetic reduction of HCK expression in bone marrow-derived cells or systemic pharmacologic inhibition of HCK activity suppresses alternative macrophage polarization and epithelial STAT3 activation, and impairs tumor growth. These data validate HCK as a molecular target for the treatment of human solid tumors harboring excessive STAT3 activity. ©2020 American Association for Cancer Research.

Citation

Ashleigh R Poh, Amy R Dwyer, Moritz F Eissmann, Ashwini L Chand, David Baloyan, Louis Boon, Michael W Murrey, Lachlan Whitehead, Megan O'Brien, Clifford A Lowell, Tracy L Putoczki, Fiona J Pixley, Robert J J O'Donoghue, Matthias Ernst. Inhibition of the SRC Kinase HCK Impairs STAT3-Dependent Gastric Tumor Growth in Mice. Cancer immunology research. 2020 Apr;8(4):428-435