Abstract
Leptin is a hormone secreted mainly by adipocytes; physiologically, it participates in the control of appetite and energy expenditure. However, it has also been linked to tumor progression in different epithelial cancers. In this review, we describe the effect of leptin on epithelial–mesenchymal transition (EMT) markers in different study models, including in vitro, in vivo, and patient studies and in various types of cancer, including breast, prostate, lung, and ovarian cancer. The different studies report that leptin promotes the expression of mesenchymal markers and a decrease in epithelial markers, in addition to promoting EMT-related processes such as cell migration and invasion and poor prognosis in patients with cancer. Finally, we report that leptin has the greatest biological relevance in EMT and tumor progression in breast, lung, prostate, esophageal, and ovarian cancer. This relationship could be due to the key role played by the enriched tumor microenvironment in adipose tissue. Together, these findings demonstrate that leptin is a key biomolecule that drives EMT and metastasis in cancer.
Highlights
The term epithelial–mesenchymal transition (EMT) was described in 1995 by Elizabeth D
The IRS/PI3K signaling pathway activates cyclic nucleotide phosphodiesterase 3B (PDE3B) enzymes, whereby PDE3B promotes the decrease in levels of cyclic adenosine monophosphate which inhibits the activity of the cAMP response element binding protein (CREB) by suppressing NPY expression through the cAMP–CREB pathway to achieve the anorexigenic effect of leptin
There is little information about the leptin-induced molecular mechanisms that regulate the growth of cholangiocarcinoma cells; evidence from in vitro studies in HuH-28 intrahepatic cholangiocarcinoma cells indicates that leptin promotes cell proliferation and migration, while in in vivo models of cholangiocarcinoma cells, leptin promotes the activation of the STAT3 and ERK1/2 signaling pathways [187]
Summary
The term epithelial–mesenchymal transition (EMT) was described in 1995 by Elizabeth D. By inducing signaling pathways that regulate cell migration and invasion [36,37] and the maintenance of cancer stem cells [38,39] and metastasis [35]. In vivo, and patient studies have demonstrated that leptin is an actor in the induction of EMT during tumor progression; the question remains: What is the mechanism for the activation of this process? The goals of this review are as follows: (1) To update the markers associated with the epithelial and mesenchymal phenotype, (2) to describe the inducers associated with EMT and tumor progression, (3) to discuss the signaling pathways induced by leptin, and (4) to report the most recent findings from in vitro, in vivo, and patient studies of the role of leptin as an inducer of EMT in cancer
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