Abstract
Leptin is a peptide hormone that has been characterized as the ligand of leptin receptor (LEPR). The observation of leptin secretion and leptin receptor expression beyond the normal tissues suggests the potentially critical roles other than its physiological function. In addition to the original function in controlling appetite and energy expenditure, leptin-mediated signaling axis through leptin receptor is multifunctional which plays role in the regulation toward broad types of cancer. Emerging evidences has indicated leptin's function in promoting several processes which are relevant to cancer progression including cell proliferation, metastasis, angiogenesis and drug resistance. We relatively display leptin and leptin receptor expression levels in pan-cancer panel based on the transcriptome analysis via dataset The Cancer Genome Atlas (TCGA), and show the clinical association of the axis in predicting cancer prognosis. The results indicate the pathological impacts of this axis on many types of cancer. This review mainly focuses on leptin-mediated effects and its downstream signaling related to the progression of cancers, and displays the clinical significance of this axis including the impact on cancer patient survival.
Highlights
Leptin is the product of Ob (LEP) gene cloned in1994 by Friedman and colleagues, and was called leptin after the Greek “leptos” meaning thin [1]
Emerging studies pointed out its expression in broad range of cancer types and the leptin-dependent signaling in regulating several important factors in cancer progression including tumor proliferation, metastasis, angiogenesis and drug resistance
We demonstrated the relative expression level of leptin and leptin receptor in a pan-cancer panel, and revealed the dramatic upregulation of the leptin-leptin receptor axis in breast cancer, head and neck cancer, lung cancer, ovarian cancer and pancreatic cancer, suggesting the potential critical role of this signaling node in tumor progression
Summary
Leptin is the product of Ob (LEP) gene cloned in1994 by Friedman and colleagues, and was called leptin after the Greek “leptos” meaning thin [1]. Leptin was identified as a peptide hormone released by adipocytes which primarily functions as the ligand of leptin receptor (LEPR) to regulate appetite and energy expenditure [2, 3]. The recent discovery of leptin and leptin receptor expression level beyond the traditional tissues indicates that the signaling axis has a critical role outside of its physiological function. The tissues with leptin expression include placenta, stomach, fibroblast, mammary epithelium, and skeletal muscle [4,5,6,7]. Emerging studies pointed out its expression in broad range of cancer types and the leptin-dependent signaling in regulating several important factors in cancer progression including tumor proliferation, metastasis, angiogenesis and drug resistance. We focus on the pathological function of leptin-leptin receptor in cancer, and further illustrate the clinical significance based on the correlation with cancer patient outcomes
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