Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25316
Title: Inhibition of the SRC Kinase HCK Impairs STAT3-Dependent Gastric Tumor Growth in Mice.
Austin Authors: Poh, Ashleigh R;Dwyer, Amy R;Eissmann, Moritz F ;Chand, Ashwini L;Baloyan, David;Boon, Louis;Murrey, Michael W;Whitehead, Lachlan;O'Brien, Megan;Lowell, Clifford A;Putoczki, Tracy L;Pixley, Fiona J;O'Donoghue, Robert J J;Ernst, Matthias
Affiliation: The Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne, Victoria, Australia
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
Olivia Newton-John Cancer Research Institute
Department of Pharmacology and Therapeutics, University of Melbourne, Victoria, Australia
School of Medicine and Pharmacology, The University of Western Australia, Western Australia, Australia
Bioceros BV, Utrecht, the Netherlands
University of California San Francisco, San Francisco, California
La Trobe University School of Cancer Medicine, Victoria, Australia
Issue Date: 2020
metadata.dc.date: 2020
Publication information: Cancer Immunology Research 2020; 8(4): 428-435
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 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/25316
DOI: 10.1158/2326-6066.CIR-19-0623
ORCID: 0000-0002-1245-729X
0000-0002-4388-9642
0000-0002-1571-2532
PubMed URL: 31992566
Type: Journal Article
Appears in Collections:Journal articles

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