TY - JOUR
T1 - Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells
AU - Guo, Shanchun
AU - Liu, Mingli
AU - Wang, Guangdi
AU - Torroella-Kouri, Marta
AU - Gonzalez-Perez, Ruben R.
N1 - Funding Information:
This work was partially funded by Grants from NIH/NCI 1SC1CA138658-03 ; and the Georgia Cancer Coalition Distinguished Cancer Scholar Award to R.R.G-P.; NIH/NCI 1R21CA153172-01A1 to MT-K, and facilities and support services at Morehouse School of Medicine ( NIH RR03034 and 1C06 RR18386 ) and NIH/NCRR grant 1G12RR026250-03 .
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Breast cancer stem cells
KW - Leptin
KW - Leptin antagonist
KW - Leptin signaling
KW - Tumor angiogenesis
UR - http://www.scopus.com/inward/record.url?scp=84862819412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862819412&partnerID=8YFLogxK
U2 - 10.1016/j.bbcan.2012.01.002
DO - 10.1016/j.bbcan.2012.01.002
M3 - Review article
C2 - 22289780
AN - SCOPUS:84862819412
VL - 1825
SP - 207
EP - 222
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
SN - 0304-419X
IS - 2
ER -