Inhibition of hematopoietic cell kinase activity suppresses myeloid cell-mediated colon cancer progression
- Author(s)
- Poh, AR; Love, CG; Masson, F; Preaudet, A; Tsui, C; Whitehead, L; Monard, S; Khakham, Y; Burstroem, L; Lessene, G; Sieber, O; Lowell, C; Putoczki, TL; O'Donoghue, RJ; Ernst, M;
- 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
- Research Division(s)
- Molecular Immunology; Systems Biology And Personalised Medicine; Chemical Biology; Inflammation
- PubMed ID
- 28399411
- Publisher's Version
- https://doi.org/10.1016/j.ccell.2017.03.006
- NHMRC Grants
- NHMRC/1008614, NHMRC/1016647, NHMRC/1025239,
- Terms of Use/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