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https://hdl.handle.net/2440/128316
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Type: | Journal article |
Title: | Inhibition of the SRC kinase HC impairs STAT3-dependent gastric tumor growth in mice |
Author: | Poh, A.R. Dwyer, A.R. Eissmann, M.F. Chand, A.L. Baloyan, D. Boon, L. Murrey, M.W. Whitehead, L. O'Brien, M. Lowell, C.A. Putoczki, T.L. Pixley, F.J. O'Donoghue, R.J.J. Ernst, M. |
Citation: | Cancer Immunology Research, 2020; 8(4):428-435 |
Publisher: | American Association for Cancer Research |
Issue Date: | 2020 |
ISSN: | 2326-6066 2326-6074 |
Statement of Responsibility: | Ashleigh R. Poh, Amy R. Dwyer, Moritz F. Eissmann, Ashwini L. Chand, David Baloyan, Louis Boon ... et al. |
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. |
Keywords: | Animals Mice, Transgenic Humans Mice Stomach Neoplasms Pyrimidines Pyrroles Survival Rate Macrophage Activation Phosphorylation Female Male STAT3 Transcription Factor Proto-Oncogene Proteins c-hck |
Rights: | © 2020 American Association for Cancer Research. |
DOI: | 10.1158/2326-6066.CIR-19-0623 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1025239 http://purl.org/au-research/grants/nhmrc/1079257 http://purl.org/au-research/grants/nhmrc/1081373 http://purl.org/au-research/grants/nhmrc/1092788 |
Published version: | http://dx.doi.org/10.1158/2326-6066.cir-19-0623 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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