Abstract
Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.
Highlights
The clinical discrepancy observed among different research groups might result from the differences including the human races, case numbers enrolled in each cohort, endpoint setting, quality of care in hospitals, detection platforms, random errors, and the involvement of complicated interaction networks contributing to the different outcomes in specific cancer types
The signaling axis plays a critical role in regulating several key processes in cancer progression, including cell proliferation, metastasis, angiogenesis, and drug resistance
We demonstrated the relative expression levels of leptin and leptin receptors in a pancancer panel
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Leptin (LEP), a protein hormone secreted by adipose tissues, primarily functions as the ligand of leptin receptor (LEPR) to regulate appetite and energy expenditure [1,2]. Leptin plays critical roles in the modulation of processes involving in the hormones synthesis, blood pressure, reproduction, osteogenesis, hematopoiesis, angiogenesis, and immunity [3]. The leptin receptor, encoded by LEPR, is a member of the class 1 cytokine receptor family and has been indicated to play critical roles in the pathogenesis of many malignant cancer types [1,8,9]. We integrate and summarize the current literature on this topic, focusing on evidence demonstrating leptin/leptin receptor expression levels in a broad range of cancer types together with its biological effects on the regulation of several critical processes related to cancer progression. In addition to the biological function of the leptin axis in cancer, its clinical and prognostic significance in multiple cancer types is illustrated
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