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Title: Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression.
Austin Authors: Poh, Ashleigh R;Love, Christopher G;Masson, Frederic;Preaudet, Adele;Tsui, Cary;Whitehead, Lachlan;Monard, Simon;Khakham, Yelena;Burstroem, Lotta;Lessene, Guillaume;Sieber, Oliver;Lowell, Clifford;Putoczki, Tracy L;O'Donoghue, Robert J J;Ernst, Matthias 
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Pathology and Laboratory Medicine, University of California, San Francisco, CA 94143, USA
Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC 3010, Australia
Department of Colorectal Surgery, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia
School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia
The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia
Issue Date: 10-Apr-2017
Publication information: Cancer cell 2017; 31(4): 563-575.e5
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 alternative activation of tumor-associated macrophages and the growth of colon cancer xenografts. Thus, Hck may serve as a promising therapeutic target for solid malignancies.
DOI: 10.1016/j.ccell.2017.03.006
PubMed URL: 28399411
Type: Journal Article
Subjects: SRC family kinases
Alternative macrophage polarization
Colitis-associated colon cancer
Colorectal cancer
Hematopoietic cell kinase
Mouse model
tumor microenvironment
tyrosine kinase inhibitor
Appears in Collections:Journal articles

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