Leptin Increases Motility and Integrin Up-regulation in Human Prostate Cancer Cells
Leptin Increases Motility and Integrin Up-regulation in Human Prostate Cancer Cells
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DOI：
10.1002/jcp.22455
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发表时间：
2011-05-01
影响因子：
5.6
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
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作者：
Huang, Chih-Yang;Yu, Hsin-Shan;Tang, Chih-Hsin
前列腺癌是男性中最常见的恶性肿瘤，并显示出转移到远处器官的倾向。瘦素是一种与肥胖密切相关的脂肪细胞源性细胞因子，近年来研究表明其参与了肿瘤的发生和发展。本研究的目的是调查是否瘦素与前列腺癌细胞的运动。我们发现瘦素增加了人前列腺癌细胞的迁移和这些细胞上α v β 3整合素的表达。瘦素介导的迁移和增加的整合素表达被OBR 1受体反义寡核苷酸（ODN）减弱。瘦素治疗后，胰岛素受体底物（IRS-1），磷脂酰肌醇3-激酶（PI 3 K），Akt和NF-κ B途径的激活被证明。此外，瘦素诱导的整合素表达和迁移活性被特异性抑制剂、小干扰RNA（siRNA）和IRS-1、PI 3 K、Akt和NF-κ B级联的突变体抑制。因此，本研究表明瘦素刺激人前列腺癌细胞迁移，其机制之一是通过OBR 1/IRS-1/PI 3 K/Akt/NF-κ B信号转导通路转录上调α v β 3整合素的表达。J.细胞。226：1274-1282，2011。(C)2010 Wiley-Liss，Inc.
Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Leptin, an adipocyte-derived cytokine that is closely associated with obesity, has recently been shown to be involved in carcinogenesis and cancer progression. The aim of this study was to investigate whether leptin is associated with the motility of prostate cancer cells. We found that leptin increased the migration of human prostate cancer cells and expression of alpha v beta 3 integrin on these cells. Leptin-mediated migration and increased integrin expression were attenuated by OBRl receptor antisense oligonucleotide (ODN). Activation of insulin receptor substrate (IRS-1), phosphatidylinositol 3-kinase (PI3K), Akt, and NF-kappa B pathways after leptin treatment was demonstrated. Furthermore, leptin-induced integrin expression and migration activity were inhibited by specific inhibitors; small interfering RNAs (siRNAs); and mutants of the IRS-1, PI3K, Akt, and NF-kappa B cascades. Therefore, this study shows that leptin stimulates the migration of human prostate cancer cells, one of the mechanisms underlying leptin-directed migration was transcriptional up-regulation of alpha v beta 3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-kappa B signal transduction pathway. J. Cell. Physiol. 226: 1274-1282, 2011. (C) 2010 Wiley-Liss, Inc.