Leptin and cancer: Pathogenesis and modulation

Abstract

Leptin, a product of Ob gene from adipocytes regulates appetite, energy expenditure and body mass composition by decreasing orexigenic and increasing anorexigenic neuropeptide release from hypothalamus. Research over the past few years have suggested leptin/leptin receptor dysregulation to have a role in the development of a large variety of malignancies like breast ca, thyroid ca, endometrial ca and gastrointestinal malignancies, predominantly through JAK/STAT pathway which modulates PI3K/AKT3 signaling, ERK1/2 signaling, expression of antiapoptotic proteins (like XIAP), systemic inflammation (TNF-α, IL6), angiogenic factors (VEGF) and hypoxia inducible factor-1a (HIF-1a) expression. In this review, the current understanding of leptin's role in carcinogenesis has been elaborated. Also a few agents modulating leptin signaling to inhibit cancer cell growth has been described.

Stężenia adipokin u mężczyzn z rakiem prostaty i z łagodnym przerostem prostaty

“…Leptin concentrations are increased in obese patients and it is well documented that this hormone stimulates tumor cells growth and invasion. There is a growing evidence of its role in development of colorectal, hepatocellular, breast and thyroid cancer [17]. Observation that leptin receptors have high expression in the prostate proves leptin role in pathophysiology processes [18].…”

Comparative endocrinology of leptin: Assessing function in a phylogenetic context

“…Proposed mechanisms include: increased estrogen production and decreased estrogen receptor degradation, upregulated expression of VEGF and VEGFR (Dutta et al, 2012), stimulation of cyclin D1 expression, and induction of cancer stem cell survival and pluripotency (Zheng et al, 2013, 2012) in breast cancer and colorectal cancer (Bartucci et al, 2010), and increased expression of leptin receptor leading to higher levels of the anti-apoptotic protein XIAP (Cheng et al, 2010) in thyroid cancer. Leptin receptor antagonists are being developed and could be useful tools for cancer therapeutics (Otvos and Surmacz, 2011).…”

Leptin receptor polymorphism Gln223Arg (rs1137101) in oral squamous cell carcinoma and potentially malignant oral lesions

“…Leptin (LEP) is a hormone secreted from adipocytes that plays an important role in energetic metabolism, control of food intake, and obesity through its binding to LEPR receptors (Dutta et al 2012 ). Leptin receptors are mainly found in the hypothalamus.…”