PI3Kp110-, Src-, FAK-dependent and DOCK2-independent migration and invasion of CXCL13-stimulated prostate cancer cells

Molecular Cancer

Research

Paul R. Johnson¹  Jill Suttles²  Praveen K. Sharma²  Rajesh Singh³  Shailesh Singh³  James W. Lillard³  Christelle P. El Haibi⁴ 

[1] Department of Biochemistry & Molecular Biology, University of Louisville School of Medicine, Louisville, KY, USA;Department of Microbiology & Immunology, University of Louisville School of Medicine, Louisville, KY, USA;Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA, USA;Department of of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;

关键词: Focal Adhesion Kinase;    LNCaP Cell;    SU6656;    LNCaP Cell Line;    PI3K Isoforms;   

DOI  :  10.1186/1476-4598-9-85

 received in 2009-08-13, accepted in 2010-04-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMost prostate cancer (PCa)-related deaths are due to metastasis, which is mediated in part by chemokine receptor and corresponding ligand interaction. We have previously shown that PCa tissue and cell lines express high levels of the chemokine receptor CXCR5, than compared to their normal counterparts, and interaction of CXCR5 with its specific ligand (CXCL13) promoted PCa cell invasion, migration, and differential matrix metalloproteinase (MMP) expression. This study dissects some of the molecular mechanisms following CXCL13-CXCR5 interaction that mediate PCa cell migration and invasion.ResultsUsing Western blot analysis, kinase-specific cell-based ELISAs, and migration and invasion assays, we show that PCa cell lines differentially express phosphoinositide-3 kinase (PI3K) catalytic subunit isoforms and dedicator of cytokinesis 2 (DOCK2). Specifically, we show that PC3 and normal prostatic epithelial (RWPE-1), but not LNCaP cell lines expressed DOCK2, while RWPE, PC3, and LNCaP cell lines expressed PI3K-p110α and -p110β. Moreover, PC3 selectively expressed PI3K-p110γ, but LNCaP and RWPE cell lines expressed PI3Kp110δ. CXCL13 caused CXCR5-dependent activation of the PI3Kp85α in LNCaP cells, and p85α as well as -p101 in PC3 cells. CXCL13-CXCR5 interaction regulated LNCaP and PC3 cell migration and invasion through extracellular signal-regulated kinase 1/2 (ERK1/2) activation that was primarily dependent on the PI3Kp110 isoform(s), Src, and focal adhesion kinase (FAK), but not DOCK2.ConclusionsWhile additional studies will be needed to determine the PI3K-independent (i.e., DOCK2-mediated) and -dependent events that dictate PCa cell responsiveness to CXCL13, these data provide evidence of the existence of cell type- and stimulus-specific signaling events that support migration and invasion of PCa cells.

【 授权许可】

Unknown   
© El Haibi et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.