Molecular Pathways: Adiponectin and Leptin Signaling in Cancer

Abstract

The increasing percentage of obese individuals in the population and its independent association of increased risk for the development of cancer have heightened the necessity to understand the molecular mechanisms that underlie this connection. The deregulation of adipokines in the setting of obesity and their impact on cancer progression and metastasis is one such area of research. Adipokines are bioactive proteins that mediate metabolism, inflammation, angiogenesis, and proliferation. Altered levels of adipokines or their cognate receptors in cancers can ultimately lead to an imbalance in downstream molecular pathways. Discovery of adipokine receptors in various cancers has highlighted the potential for novel therapeutic targets. Leptin and adiponectin represent two adipokines that elicit generally opposing molecular effects. Epidemiological studies have highlighted associations between increased serum leptin levels and increased tumor growth, while adiponectin exhibits an inverse correlation with cancer development. This review addresses the current level of understanding of molecular pathways activated by adiponectin and leptin to identify areas of intervention and facilitate advancement in the field.

Obesity and thyroid cancer

“…These molecules will then regulate several pathways of pivotal importance to cancers, such as the AKT/mTOR/PI3K and ERK/MAPK pathways, involved in cell growth and survival; COX2, IL1, and NFkB, related to inflammation; and VEGFs, involved in angiogenesis (Surmacz 2013). Thus, leptin interacts with several factors that participate in diverse carcinogenic stages, and its relationship with breast, prostate, colorectal, hepatocellular, pancreatic, and lung cancers, as well as thyroid cancer, has consistently been demonstrated in the literature (Dutta et al 2012, Vansaun 2013. Concerning thyroid cancers, and more specifically DTCs, leptin and OBR (LEPR) expression were first demonstrated by Cheng et al (2010b), who found them associated with a high risk of lymph node metastases.…”

Loss of Phosphatase and Tensin Homolog (PTEN) Induces Leptin-mediated Leptin Gene Expression

“…LEP signals are pro-angiogenic, pro-inflammatory, and mitogenic and are mediated via multiple cross-regulatory pathways involving oncogenes, cytokines, and growth factors, driving growth of solid tumors (19,20). LEP activates JAK2/STAT3, MAPK/ERK1/2, and PI3K/AKT signaling pathways (2,21).…”

Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation

“…Breast cancer is one of the most common malignancies in women worldwide, with multiple risk factors identified, including differential expression of adipocytokines (1,2). Visfatin, also known as nicotinamide phosphoribosyltransferase (NAMPT) or pre-B-cell colony-enhancing factor (PBEF), is a 52 kDa adipocytokine discovered both intracellularly and extracellularly (3).…”