Inhibition of hematopoietic cell kinase activity suppresses myeloid cell-mediated colon cancer progression
Details
Publication Year 2017-04-10, Volume 31, Issue #4, Page 563-575 e5
Journal Title
Cancer Cell
Publication Type
Journal Article
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.
Publisher
Cell Press
WEHI Research Division(s)
Molecular Immunology; Systems Biology And Personalised Medicine; Chemical Biology; Inflammation
PubMed ID
28399411
NHMRC Grants
NHMRC/1008614 NHMRC/1016647 NHMRC/1025239
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-05-02 03:01:30
Last Modified: 2017-05-09 09:48:38
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