首页> 外文期刊>Biological chemistry >Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway.
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Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway.

机译:组织激肽释放酶通过蛋白酶激活的受体1依赖性信号通路促进前列腺癌细胞的迁移和侵袭。

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We recently demonstrated that tissue kallikrein (TK) promotes keratinocyte migration through activation of protease-activated receptor-1 (PAR(1)) and transactivation of the epi-dermal growth factor receptor (EGFR). In this study, we investigated the potential role of PAR(1) in mediating the effect of TK on cancer cell migration, invasion and proliferation. Our results show that TK promotes DU145 prostate cancer cell migration in a concentration-dependent manner, but has no effect on A549 lung cancer cells. Active TK markedly increases DU145 cell migration and invasion, which are blocked by aprotinin but minimally affected by icatibant; kinin treatment has little effect. TK-induced cell migration and invasion are abolished by inhibition of PAR(1) using a pharmacological inhibitor or RNA interference. The effect of TK on cell migration and invasion are also blocked by inhibitors of protein kinase C, c-Src, matrix metalloproteinase, EGFR and extracellular signal-regulated kinase (ERK). Moreover, TK stimulates ERK phosphorylation, which is inhibited by an EGFR antagonist. Additionally, TK but not kinin stimulates DU145 cell proliferation through activation of the kinin B2 receptor, but not PAR(1) and EGFR. These results indicate differential signaling pathways mediated by TK in promoting prostate cancer cell migration and invasion via PAR(1) activation, and proliferation via kinin B2 receptor stimulation.
机译:我们最近证明组织激肽释放酶(TK)通过激活蛋白酶激活受体1(PAR(1))和表皮生长因子受体(EGFR)的反式激活来促进角质形成细胞迁移。在这项研究中,我们调查了PAR(1)在介导TK对癌细胞迁移,侵袭和增殖的影响中的潜在作用。我们的结果表明,TK以浓度依赖的方式促进DU145前列腺癌细胞的迁移,但对A549肺癌细胞没有影响。活性TK显着增加DU145细胞的迁移和侵袭,其被抑肽酶阻断,但受伊卡替丁影响最小;激肽治疗效果不明显。通过使用药理抑制剂或RNA干扰抑制PAR(1),消除了TK诱导的细胞迁移和侵袭。蛋白激酶C,c-Src,基质金属蛋白酶,EGFR和细胞外信号调节激酶(ERK)的抑制剂也阻断了TK对细胞迁移和侵袭的影响。此外,TK刺激ERK磷酸化,这被EGFR拮抗剂抑制。此外,TK可通过激肽B2受体而不是PAR(1)和EGFR的活化来刺激DU145细胞增殖。这些结果表明由TK介导的不同信号通路通过PAR(1)激活促进前列腺癌细胞的迁移和侵袭,并通过激肽B2受体刺激来促进增殖。

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