RT Journal Article
SR Electronic
T1 Action of the Src Family Kinase Inhibitor, Dasatinib (BMS-354825), on Human Prostate Cancer Cells
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 9185
OP 9189
DO 10.1158/0008-5472.CAN-05-1731
VO 65
IS 20
A1 Nam, Sangkil
A1 Kim, Donghwa
A1 Cheng, Jin Q.
A1 Zhang, Shumin
A1 Lee, Ji-Hyun
A1 Buettner, Ralf
A1 Mirosevich, Janni
A1 Lee, Francis Y.
A1 Jove, Richard
YR 2005
UL http://cancerres.aacrjournals.org/content/65/20/9185.abstract
AB Src family kinases (SFK) are currently being investigated as targets for treatment strategies in various cancers. The novel SFK/Abl inhibitor, dasatinib (BMS-354825), is a promising therapeutic agent with oral bioavailability. Dasatinib has been shown to inhibit growth of Bcr-Abl–dependent chronic myeloid leukemia xenografts in nude mice. Dasatinib also has been shown to have activity against cultured human prostate and breast cancer cells. However, the molecular mechanism by which dasatinib acts on epithelial tumor cells remains unknown. In this study, we show that dasatinib blocks the kinase activities of the SFKs, Lyn, and Src, in human prostate cancer cells at low nanomolar concentrations. Moreover, focal adhesion kinase and Crk-associated substrate (p130CAS) signaling downstream of SFKs are also inhibited at similar concentrations of dasatinib. Consistent with inhibition of these signaling pathways, dasatinib suppresses cell adhesion, migration, and invasion of prostate cancer cells at low nanomolar concentrations. Therefore, dasatinib has potential as a therapeutic agent for metastatic prostate cancers harboring activated SFK and focal adhesion kinase signaling. ©2005 American Association for Cancer Research.