Role of leptin and leptin receptors in hematological malignancies

Uddin, Shahab; Mohammad, Ramzi M.

doi:10.3109/10428194.2015.1063145

Cited by 14 publications

(7 citation statements)

References 93 publications

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“…These results support findings of another study where enhanced expression of Ob-R was detected in biopsies of patients with ovarian cancer [70]. Furthermore, Ob-R overexpression is linked to aggressive behavior in many cancers including colon cancer, papillary thyroid and diffuse large B-cell lymphoma [16,71,72]. The aggressive phenotype of these malignancies can be explained by a strong association of leptin/Ob-R with antiapoptotic signaling including PI3K/ AKT and MAP kinase [32,34,38,40,58,73].…”

Section: Leptin and Ovarian Carcinogenesissupporting

confidence: 88%

Oncogenic role of dysregulated leptin signaling in the pathogenesis of ovarian cancer

et al. 2019

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Leptin, a pleiotropic hormone is produced by adipose tissues and plays a critical role in various biological functions. Leptin mediates its function through interaction with specific receptors. The leptin-receptor interaction modulates activation of a number of signaling pathways, such as JAK-STAT, PI3-Kinase-AKT and MAP kinases. Recently, deregulated leptin-mediated signaling has been shown in many cancers including ovarian cancer. A number of studies have shown a link between obesity and carcinogenesis of different cancers via leptin deregulated signaling pathways. In this review, we highlighted the role of deregulated leptin receptor-mediated signaling in the etiology of ovarian cancer.

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Section: Leptin and Ovarian Carcinogenesissupporting

confidence: 88%

Oncogenic role of dysregulated leptin signaling in the pathogenesis of ovarian cancer

et al. 2019

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“…Since miR-4443 was up-regulated following both leptin and insulin treatment, we hypothesized that its promoter or enhancer regions may contain the CCAAT motif, which binds transcription factors from the CCAAT-enhancer-binding proteins (C/EBP) family, that act downstream of MEK1/2 in leptin and insulin signaling [3, 40–43] and were previously described as up-regulated by both insulin and leptin [44, 45]. To investigate this possibility, a 10 kb region of the human genomic sequence upstream of pre-miR-4443, which contains no other known genes on the same (plus) strand, was analyzed using the Cister algorithm [33].…”

Section: Resultsmentioning

confidence: 99%

Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells

Meerson

Yehuda

2016

BMC Cancer

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BackgroundObesity is a risk factor for colorectal cancer (CRC). Normal and tumor cells respond to metabolic hormones, such as leptin and insulin. Thus, obesity-associated resistance to these hormones likely leads to changes in gene expression and behavior of tumor cells. However, the mechanisms affected by leptin and insulin signaling in CRC cells remain mostly unknown.MethodsWe hypothesized that microRNAs (miRNAs) are involved in the regulation of tumorigenesis-related gene expression in CRC cells by leptin and insulin. To test this hypothesis, miRNA levels in the CRC-derived cell lines HCT-116, HT-29 and DLD-1 were profiled, following leptin and insulin treatment. Candidate miRNAs were validated by RT-qPCR. Predicted miRNA targets with known roles in cancer, were validated by immunoblots and reporter assays in HCT-116 cells. Transfection of HCT-116 cells with candidate miRNA mimic was used to test in vitro effects on proliferation and invasion.ResultsOf ~800 miRNAs profiled, miR-4443 was consistently up-regulated by leptin and insulin in HCT-116 and HT-29, but not in DLD-1, which lacked normal leptin receptor expression. Dose response experiments showed that leptin at 100 ng/ml consistently up-regulated miR-4443 in HCT-116 cells, concomitantly with a significant decrease in cell invasion ability. Transfection with miR-4443 mimic decreased invasion and proliferation of HCT-116 cells. Moreover, leptin and miR-4443 transfection significantly down-regulated endogenous NCOA1 and TRAF4, both predicted targets of miR-4443 with known roles in cancer metastasis. miR-4443 was found to directly regulate TRAF4 and NCOA1, as validated by a reporter assay. The up-regulation of miR-4443 by leptin or insulin was attenuated by the inhibition of MEK1/2.ConclusionsOur findings suggest that miR-4443 acts in a tumor-suppressive manner by down-regulating TRAF4 and NCOA1 downstream of MEK-C/EBP-mediated leptin and insulin signaling, and that insulin and/or leptin resistance (e.g. in obesity) may suppress this pathway and increase the risk of metastatic CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2938-1) contains supplementary material, which is available to authorized users.

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“…The role of leptin in tumorigenesis was suggested by the high expression of the leptin receptor (ObR) in several cancer cells, such as breast, stomach, colon, ovarian cancers and leukemia [ 52 – 56 ]. In addition, the fact that leptin secretion is clearly up-regulated in obesity contributes to generate significant interest around this adipokine [ 57 ].…”

Section: Introductionmentioning

confidence: 99%

The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance

Duong¹,

et al. 2017

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Growing evidence has raised the important roles of adipocytes as an active player in the tumor microenvironment. In many tumors adipocytes are in close contact with cancer cells. They secrete various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Moreover, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, has been established as a risk factor for cancer incidence and cancer-related mortality. In this review, we summarize the mechanisms of the adipocyte-cancer cell crosstalk in both obese and lean conditions as well as its impact on cancer cell growth, local invasion, metastatic spread and resistance to treatments. Better characterization of cancer-associated adipocytes and the key molecular events in the adipocyte-cancer cell crosstalk will provide insights into tumor biology and suggest efficient therapeutic opportunities.

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Role of leptin and leptin receptors in hematological malignancies

Cited by 14 publications

References 93 publications

Oncogenic role of dysregulated leptin signaling in the pathogenesis of ovarian cancer

Oncogenic role of dysregulated leptin signaling in the pathogenesis of ovarian cancer

Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells

The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance

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