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

被引:116
作者
Guo, Shanchun [1 ]
Liu, Mingli [1 ]
Wang, Guangdi [2 ]
Torroella-Kouri, Marta [3 ]
Gonzalez-Perez, Ruben R. [1 ]
机构
[1] Morehouse Sch Med, Atlanta, GA 30310 USA
[2] Xavier Univ Louisiana, Dept Chem, New Orleans, LA 70125 USA
[3] Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2012年 / 1825卷 / 02期
关键词
Leptin; Breast cancer; Tumor angiogenesis; Breast cancer stem cells; Leptin antagonist; Leptin signaling; LEUKEMIA INHIBITORY FACTOR; ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; HUMAN ENDOMETRIAL CANCER; INTERLEUKIN-1 RECEPTOR ANTAGONIST; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; PAPILLARY THYROID-CARCINOMA; REGULATED GENE-EXPRESSION; ACTIVATED PROTEIN-KINASE; TRANSCRIPTION; STAT3;
D O I
10.1016/j.bbcan.2012.01.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:207 / 222
页数:16
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