Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22534
Title: Inhibition of the SRC kinase HCK impairs STAT3-dependent gastric tumor growth in mice.
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 Jj;Ernst, Matthias
Affiliation: Cancer and Inflammation, Olivia Newton-John Cancer Research Institute and School of Cancer Medicine at La Trobe University
School of Biomedical Sciences, University of Western Australia
Masonic Cancer Center, University of Minnesota
Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute
Cancer and Inflammation, Olivia Newton-John Cancer Research Institute and School of Cancer Medicine at La Trobe University
Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine
Bioceros, CM Utrecht
Medical Biology, The Walter and Eliza Hall Institute
Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine
Laboratory Medicine, University of California, San Francisco
Inflammation Division, Walter and Eliza Hall Institute of Medical Research
Department of Pharmacology and Therapeutics, University of Melbourne
Issue Date: 28-Jan-2020
EDate: 2020
Citation: Cancer immunology research 2020-01-28
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22534
DOI: 10.1158/2326-6066.CIR-19-0623
ORCID: 0000-0002-1245-729X
0000-0002-4388-9642
0000-0002-1571-2532
0000-0002-6399-1177
PubMed URL: 31992566
Type: Journal Article
Appears in Collections:Journal articles

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