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Title: Hematopoietic cell kinase (HCK) as a therapeutic target in immune cancer cells
Authors: Poh, Ashleigh R;O'Donoghue, Robert J J;Ernst, Matthias
Issue Date: 30-Jun-2015
EDate: 2015-06-10
Citation: Oncotarget 2015; 6(18): 15751-15771
Abstract: The hematopoietic cell kinase (HCK) is a member of the SRC family of cytoplasmic tyrosine kinases (SFKs), and is expressed in cells of the myeloid and B-lymphocyte cell lineages. Excessive HCK activation is associated with several types of leukemia and enhances cell proliferation and survival by physical association with oncogenic fusion proteins, and with functional interactions with receptor tyrosine kinases. Elevated HCK activity is also observed in many solid malignancies, including breast and colon cancer, and correlates with decreased patient survival rates. HCK enhances the secretion of growth factors and pro-inflammatory cytokines from myeloid cells, and promotes macrophage polarization towards a wound healing and tumor-promoting alternatively activated phenotype. Within tumor associated macrophages, HCK stimulates the formation of podosomes that facilitate extracellular matrix degradation, which enhance immune and epithelial cell invasion. By virtue of functional cooperation between HCK and bona fide oncogenic tyrosine kinases, excessive HCK activation can also reduce drug efficacy and contribute to chemo-resistance, while genetic ablation of HCK results in minimal physiological consequences in healthy mice. Given its known crystal structure, HCK therefore provides an attractive therapeutic target to both, directly inhibit the growth of cancer cells, and indirectly curb the source of tumor-promoting changes in the tumor microenvironment.
ORCID: 0000-0002-6399-1177
PubMed URL:
Type: Journal Article
Subjects: SRC family kinases
Hematopoietic cell kinase
SFK inhibitors
Appears in Collections:Journal articles

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