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Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression

Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression

Ashleigh R Poh, Christopher G Love, Frederick Masson, Adele Preaudet, Cary Tsui, Lachlan Whitehead, Simon Monard, Yelena Khakham, Lotta Burstroem, Guillaume Lessene, Oliver Sieber, Clifford Lowell, Tracy L Putoczki, etc.

Cancer Cell. 2017 Apr 10;31(4):563-575.e5.

PMID: 28399411

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415154	Hck human			Price

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