CXCL5/ENA78 Increased Cell Migration and Epithelial-to-Mesenchymal Transition of Hormone-Independent Prostate Cancer by Early Growth Response-1/Snail Signaling Pathway
CXCL5/ENA78 Increased Cell Migration and Epithelial-to-Mesenchymal Transition of Hormone-Independent Prostate Cancer by Early Growth Response-1/Snail Signaling Pathway
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DOI：
10.1002/jcp.22445
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发表时间：
2011-05-01
影响因子：
5.6
通讯作者：
Hsu, Ya-Ling
中科院分区：
文献类型：
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作者：
Kuo, Po-Lin;Chen, Yen-Hsu;Hsu, Ya-Ling
对激素治疗有抵抗力的前列腺癌更具侵袭性，并且比雄激素依赖性前列腺癌更有能力扩散到其他器官。此外，这种类型的前列腺癌对目前形式的化疗也具有高度抗性。这项研究分析了CXCL 5/ENA 78，它在雄激素非依赖性前列腺癌中高度表达，并负责两种雄激素非依赖性前列腺癌细胞系中的细胞迁移和上皮向间质转化。CXCL 5/ENA 78对PC-3和DU 145癌症进展的诱导与Raf/MEK/ERK活化增加以及早期生长反应-1（Egr-1）和Snail的上调相关。阻断Egr-1可降低Snail上调和细胞迁移，表明Egr-1在CXCL 5/ENA 78介导的Snail增强和细胞迁移中是必需的。此外，Egr-1 siRNA还能降低CXCL 5/ENA 78对p27抑制、Cdk 4诱导和细胞增殖的影响，提示Egr-1也参与了CXCL 5/ENA 78介导的细胞生长。此外，通过siRNA阻断ERK 1/2抑制CXCL 5/ENA 78诱导的Egr-1增强、细胞迁移和增殖。我们的研究表明，抑制CXCL 5/ENA 78介导的ERK/Egr-1/Snail信号转导是雄激素非依赖性前列腺癌的一个有吸引力的治疗靶点。J.细胞。226：1224-1231，2011。(C)2010 Wiley-Liss，Inc.
Prostate cancers that are resistant to hormone therapy are more invasive and have greater ability to spread to other organs than androgen-dependent prostate cancers. Furthermore, this type of prostate cancer is also highly resistant to current forms of chemotherapy. This study analyzed CXCL5/ENA78, which is highly expressed in androgen-independent prostate cancers, and is responsible for cell migration and epithelial-to-mesenchymal transition in two androgen-independent prostate cancer cell lines. Inducement of PC-3 and DU145 cancer progression by CXCL5/ENA78 is associated with increased Raf/MEK/ERK activation, and the upregulation of early growth response-1 (Egr-1) and Snail. Blockade of Egr-1 decreased Snail upregulation and cell migration, indicating that Egr-1 is required in CXCL5/ENA78-mediated Snail enhancement and cell migration. In addition, Egr-1 siRNA also decreased the effect of CXCL5/ENA78 on p27 inhibition, Cdk4 induction and cell proliferation, suggesting Egr-1 is also involved in CXCL5/ENA78-mediated cell growth. Moreover, blocking ERK1/2 by siRNA suppressed CXCL5/ENA78-induced Egr-1 enhancement, cell migration, and proliferation. Our study suggests that inhibition of CXCL5/ENA78-mediated ERK/Egr-1/Snail signaling is an attractive therapeutic target for androgen-independent prostate cancer. J. Cell. Physiol. 226: 1224-1231, 2011. (C) 2010 Wiley-Liss, Inc.