| First Author | Poh AR | Year | 2020 |
| Journal | Cancer Immunol Res | Volume | 8 |
| Issue | 4 | Pages | 428-435 |
| PubMed ID | 31992566 | Mgi Jnum | J:298542 |
| Mgi Id | MGI:6480235 | Doi | 10.1158/2326-6066.CIR-19-0623 |
| Citation | Poh AR, et al. (2020) Inhibition of the SRC Kinase HCK Impairs STAT3-Dependent Gastric Tumor Growth in Mice. Cancer Immunol Res 8(4):428-435 |
| abstractText | Persistent activation of the latent transcription factor STAT3 is observed in gastric tumor epithelial and immune cells and is associated with a poor patient prognosis. Although targeting STAT3-activating upstream kinases offers therapeutically viable targets with limited specificity, direct inhibition of STAT3 remains challenging. Here we provide functional evidence that myeloid-specific hematopoietic cell kinase (HCK) activity can drive STAT3-dependent epithelial tumor growth in mice and is associated with alternative macrophage activation alongside matrix remodeling and tumor cell invasion. Accordingly, genetic reduction of HCK expression in bone marrow-derived cells or systemic pharmacologic inhibition of HCK activity suppresses alternative macrophage polarization and epithelial STAT3 activation, and impairs tumor growth. These data validate HCK as a molecular target for the treatment of human solid tumors harboring excessive STAT3 activity. |
