Leptin Signaling in Breast Cancer: An Overview
Leptin Signaling in Breast Cancer: An Overview
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DOI：
10.1002/jcb.21911
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发表时间：
2008-11-01
影响因子：
4
通讯作者：
Normanno, Nicola
中科院分区：
文献类型：
--
作者：
Cirillo, Donatella;Rachiglio, Anna Maria;Normanno, Nicola
脂肪细胞衍生的肽瘦素通过与特异性膜受体结合而起作用，迄今为止已鉴定出其中六种亚型（obRa-f）。瘦素与其受体的结合诱导不同信号传导途径的激活，包括JAK/STAT、MAPK、IRS 1和SOCS 3信号传导途径。由于肥胖个体中瘦素的循环水平升高，并且超重已被证明会增加绝经后妇女患乳腺癌的风险，因此有几项研究探讨了瘦素在乳腺癌中的作用。瘦素及其受体的表达已被证明发生在乳腺癌细胞系和人原发性乳腺癌。瘦素能够通过激活Jak/STAT 3、ERK 1/2和/或PI 3 K途径诱导乳腺癌细胞的生长，并且能够通过诱导血管内皮生长因子（VEGF）的表达来介导血管生成。此外，瘦素诱导ErbB-2的反式激活，并在三阴性乳腺癌细胞中与胰岛素样生长因子-1（IGF-1）相互作用以反式激活表皮生长因子受体（EGFR），从而促进侵袭和迁移。瘦素也可以影响雌激素受体（ER）阳性乳腺癌细胞的生长，通过刺激芳香化酶的表达，从而增加雌激素水平通过雄激素的芳构化，并通过诱导MAPK依赖性激活ER。两者合计，这些研究结果表明，瘦素系统可能在乳腺癌的发病机制和进展中发挥重要作用，它可能是一个新的目标，乳腺癌的治疗干预。J.细胞。105：956-964，2008. (c)2008威利利斯公司
The adipocyte-derived peptide leptin acts through binding to specific membrane receptors, of which six isoforms (obRa-f) have been identified up to now. Binding of leptin to its receptor induces activation of different signaling pathways, including the JAK/STAT, MAPK, IRS1, and SOCS3 signaling pathways. Since the circulating levels of leptin are elevated in obese individuals, and excess body weight has been shown to increase breast cancer risk in postmenopausal women, several studies addressed the role of leptin in breast cancer. Expression of leptin and its receptors has been demonstrated to occur in breast cancer cell lines and in human primary breast carcinoma. Leptin is able to induce the growth of breast cancer cells through activation of the Jak/STAT3, ERK1/2, and/or PI3K pathways, and can mediate angiogenesis by inducing the expression of vascular endothelial growth factor (VEGF). In addition, leptin induces transactivation of ErbB-2, and interacts in triple negative breast cancer cells with insulin like growth factor-1 (IGF-1) to transactivate the epidermal growth factor receptor (EGFR), thus promoting invasion and migration. Leptin can also affect the growth of estrogen receptor (ER)-positive breast cancer cells, by stimulating aromatase expression and thereby increasing estrogen levels through the aromatization of androgens, and by inducing MAPK-dependent activation of ER. Taken together, these findings suggest that the leptin system might play an important role in breast cancer pathogenesis and progression, and that it might represent a novel target for therapeutic intervention in breast cancer. J. Cell. Biochem. 105: 956-964, 2008. (c) 2008 Wiley-Liss, Inc.