Csk Homologous Kinase, a Potential Regulator of CXCR4-mediated Breast Cancer Cell Metastasis
Annual rept. 1 Aug 2009-31 Jul 2010
PITTSBURGH UNIV PA
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Metastasis is still a major cause of morbidity and mortality in breast cancer patients. However, current therapy still fails to kill migrating metastasizing breast cancer cells. CXCR4 is a chemokine receptor implicated in the metastatic migration of breast cancer cells and its expression predicts poor prognosis in breast cancer patients. Several studies have revealed that the block of CXCR4 functions prevented metastasis in breast cancer. However, CXCR4 is expressed on the surface of several tissues and there are some concerns about using drugs to target CXCR4. In fact, AMD-3100, a CXCR4 receptor blocker, exerted unfavorable side effects in a clinical trial. Therefore, it is necessary to develop tissue-specific and tumor specific CXCR4 blockers. Because Csk Homologous kinase CHK is a negative regulator of CXCR4 and preferentially expressed in breast cancer cells, modulating CHK activity may facilitate the development of side-effect-free treatment for metastatic breast cancer. Our aim is to identify the functional role of CHK in breast cancer metastasis using in vivo xenograft model systems. With resulting information from this study, we may devise treatments that selectively target metastatic breast cancer cells.
- Anatomy and Physiology
- Medicine and Medical Research