PI3Kp110-, Src-, FAK-dependent and DOCK2-independent migration and invasion of CXCL13-stimulated prostate cancer cells.
PI3Kp110-, Src-, FAK-dependent and DOCK2-independent migration and invasion of CXCL13-stimulated prostate cancer cells.
复制标题
DOI：
10.1186/1476-4598-9-85
复制
发表时间：
2010-04-22
期刊：
影响因子：
37.3
通讯作者：
Lillard JW Jr
中科院分区：
文献类型：
--
作者：
El Haibi CP;Sharma PK;Singh R;Johnson PR;Suttles J;Singh S;Lillard JW Jr
大多数前列腺癌（PCa）相关的死亡是由于转移，这是部分介导的趋化因子受体和相应的配体相互作用。我们以前已经表明，PCa组织和细胞系表达高水平的趋化因子受体CXCR 5，比他们的正常同行，和CXCR 5与其特异性配体（CXCL 13）的相互作用促进PCa细胞的侵袭，迁移，和差异基质金属蛋白酶（MMP）的表达。本研究剖析了CXCL 13-CXCR 5相互作用后介导PCa细胞迁移和侵袭的一些分子机制。使用蛋白质印迹分析，激酶特异性细胞为基础的ELISA，迁移和侵袭试验，我们表明，PCa细胞株差异表达磷脂酰肌醇-3激酶（PI 3 K）催化亚基亚型和细胞分裂奉献者2（DOCK 2）。具体来说，我们发现PC 3和正常前列腺上皮细胞（RWPE-1）表达DOCK 2，但LNCaP细胞系不表达DOCK 2，而RWPE、PC 3和LNCaP细胞系表达PI 3 K-p110 α和-p110β。此外，PC 3选择性表达PI 3 K-p110 γ，而LNCaP和RWPE细胞系表达PI 3 Kp 110 δ。CXCL 13可引起LNCaP细胞中PI 3 Kp 85 α和PC 3细胞中p85 α以及-p101的CXCR 5依赖性激活。CXCL 13-CXCR 5相互作用通过细胞外信号调节激酶1/2（ERK 1/2）激活调节LNCaP和PC 3细胞的迁移和侵袭，ERK 1/2激活主要依赖于PI 3 Kp 110亚型、Src和粘着斑激酶（FAK），但不依赖于DOCK 2。虽然需要额外的研究来确定PI 3 K独立性（即，DOCK 2介导的）和依赖性事件，决定PCa细胞对CXCL 13的反应，这些数据提供了证据的存在细胞类型和刺激特异性信号传导事件，支持迁移和侵袭的PCa细胞。
Most 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. Using 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. While 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.
登录
查看更多内容
DOI：
10.1097/01.blo.0000093840.72468.e1
发表时间：
2003-10-01
影响因子：
4.2
作者：
Clark, PE;Tord, FM
通讯作者：
Tord, FM
影响因子：
6.2
作者：
Clines, Gregory A.;Guise, Theresa A.
通讯作者：
Guise, Theresa A.
影响因子：
3.4
作者：
Chang, CC;Sun, W;Trosko, JE
通讯作者：
Trosko, JE
影响因子：
7.8
作者：
Kunisaki, Yuya;Nishikimi, Akihiko;Tanaka, Yoshihiko;Takii, Ryosuke;Noda, Mayuko;Inayoshi, Ayumi;Watanabe, Ken-ichi;Sanematsu, Fumiyuki;Sasazuki, Takehiko;Sasaki, Takehiko;Fukui, Yoshinori
通讯作者：
Fukui, Yoshinori
影响因子：
5.6
作者：
Lisignoli, G;Toneguzzi, S;Facchini, A
通讯作者：
Facchini, A