Graduate Institute of Basic Medical Science, China Medical University and Hospital, Taichung, Taiwan.
J Cell Physiol. 2011 May;226(5):1274-82. doi: 10.1002/jcp.22455.
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 αvβ3 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-κB 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-κB 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 αvβ3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-κB signal transduction pathway.
前列腺癌是男性最常见的恶性肿瘤，易发生远处转移。瘦素是一种与肥胖密切相关的脂肪细胞衍生细胞因子，最近发现其与肿瘤发生和癌症进展有关。本研究旨在探讨瘦素是否与前列腺癌细胞的运动有关。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 αvβ3 整合素的表达。OBR1 受体反义寡核苷酸 (ODN) 可减弱瘦素介导的迁移和整合素表达增加。瘦素处理后，胰岛素受体底物 (IRS-1)、磷脂酰肌醇 3-激酶 (PI3K)、Akt 和 NF-κB 途径被激活。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、PI3K、Akt 和 NF-κB 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的迁移，瘦素诱导的迁移的一种机制是通过 OBR1/IRS-1/PI3K/Akt/NF-κB 信号转导通路转录上调 αvβ3 整合素表达。
