Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells

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• 作者：Shanchun Guo^a ; Mingli Liu^a ; Guangdi Wang^b ; Marta Torroella-Kouri^c ; Ruben R. Gonzalez-Perez^a ; ^{rgonzalez@msm.edu}
• 关键词：Leptin ; Breast cancer ; Tumor angiogenesis ; Breast cancer stem cells ; Leptin antagonist ; Leptin signaling
• 刊名：Biochimica et Biophysica Acta (BBA)/Reviews on Cancer
• 出版年：2012
• 期刊代码：23_0304419x
• 类别：bio
• 出版时间：April, 2012
• 卷：1825
• 期：2
• 页码：207-222
• 文件大小：997 K

摘要

Significant correlations between obesity and incidence of various cancers have been reported. Obesity, considered a mild inflammatory process, is characterized by a high level of secretion of several cytokines from adipose tissue. These molecules have disparate effects, which could be relevant to cancer development. Among the inflammatory molecules, leptin, mainly produced by adipose tissue and overexpressed with its receptor (Ob-R) in cancer cells is the most studied adipokine. Mutations of leptin or Ob-R genes associated with obesity or cancer are rarely found. However, leptin is an anti-apoptotic molecule in many cell types, and its central roles in obesity-related cancers are based on its pro-angiogenic, pro-inflammatory and mitogenic actions. Notably, these leptin actions are commonly reinforced through entangled crosstalk with multiple oncogenes, cytokines and growth factors. Leptin-induced signals comprise several pathways commonly triggered by many cytokines (i.e., canonical: JAK2/STAT; MAPK/ERK1/2 and PI-3K/AKT1 and, non-canonical signaling pathways: PKC, JNK and p38 MAP kinase). Each of these leptin-induced signals is essential to its biological effects on food intake, energy balance, adiposity, immune and endocrine systems, as well as oncogenesis. This review is mainly focused on the current knowledge of the oncogenic role of leptin in breast cancer. Additionally, leptin pro-angiogenic molecular mechanisms and its potential role in breast cancer stem cells will be reviewed. Strict biunivocal binding-affinity and activation of leptin/Ob-R complex makes it a unique molecular target for prevention and treatment of breast cancer, particularly in obesity contexts.