Journal article
Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression
AR Poh, CG Love, F Masson, A Preaudet, C Tsui, L Whitehead, S Monard, Y Khakham, L Burstroem, G Lessene, O Sieber, C Lowell, TL Putoczki, RJJ O'Donoghue, M Ernst
Cancer Cell | CELL PRESS | Published : 2017
Abstract
Aberrant activation of the SRC family kinase hematopoietic cell kinase (HCK) triggers hematological malignancies as a tumor cell-intrinsic oncogene. Here we find that high HCK levels correlate with reduced survival of colorectal cancer patients. Likewise, increased Hck activity in mice promotes the growth of endogenous colonic malignancies and of human colorectal cancer cell xenografts. Furthermore, tumor-associated macrophages of the corresponding tumors show a pronounced alternatively activated endotype, which occurs independently of mature lymphocytes or of Stat6-dependent Th2 cytokine signaling. Accordingly, pharmacological inhibition or genetic reduction of Hck activity suppresses alter..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
We thank the WEHI Flow Cytometry, Animal Facility and Histology Department for excellent technical assistance. This work was made possible through Victorian State Government Operational Infrastructure Support, the Australian Cancer Research Foundation, the National Health and Medical Research Council (NHMRC) of Australia project grants 1008614, 1016647, and 1025239, the Victorian Cancer Agency grant ECSG13041, and the RFA-UD from La Trobe University. M.E. also received funding from Ludwig Cancer Research. A.R.P. is supported by an Australian Post-Graduate Award PhD Scholarship and Cancer Therapeutics CTx PhD Top-Up scholarship. M.E. and O.S. are Research Fellows of the NHMRC.