Inhibition of the SRC kinase HCK impairs STAT3-dependent gastric tumor growth in mice
Journal Title
Cancer Immunology Research
Publication Type
Journal epub ahead of print
Abstract
Persistent activation of the latent transcription factor STAT3 is observed in gastric tumor epithelial and immune cells and is associated with a poor patient prognosis. 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, 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.
Publisher
AACR
WEHI Research Division(s)
Advanced Technology And Biology; Personalised Oncology
PubMed ID
31992566
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-05-04 11:46:56
Last Modified: 2020-05-04 02:24:37
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