Expression of AdipoR1 and AdipoR2 Receptors as Leptin-Breast Cancer Regulation Mechanisms

Mociño-Rodríguez, Martha Daniela; Benítez, Jonnathan Guadalupe Santillán; Dozal-Domínguez, David Salomón; Hernández-Navarro, María Dolores; Flores-Merino, Miriam V.; Sandoval-Cabrera, Antonio; Vázquez, Francisco Javier García

doi:10.1155/2017/4862016

Cited by 12 publications

(12 citation statements)

References 51 publications

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“…Interestingly, synergistic pathway cross-talk most likely exists between the STAT3 and PPARA as they converge on upregulation of nuclear expression of CPT1 [228,229] driving FAO as an energy source in breast cancer-adipose associations. While adiponectin signaling functionally inhibits CPT1 activity (Figure 3), and has been correlated with of inhibition of STAT3 signalling in cancer, the differential expression of adiponectin receptors in the presence of leptin may reduce this inhibition, allowing for STAT3 mediation of adipocytokine signalling and promotion of breast cancer phenotypes allowing adipose tissue to create a fostering niche for cancer to thrive [230][231][232].…”

Section: Of 24mentioning

confidence: 99%

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

Kadye

Stoffels

Fanucci

et al. 2020

Cells

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Metabolic remodelling of the tumour microenvironment is a major mechanism by which cancer cells survive and resist treatment. The pro-oncogenic inflammatory cascade released by adipose tissue promotes oncogenic transformation, proliferation, angiogenesis, metastasis and evasion of apoptosis. STAT3 has emerged as an important mediator of metabolic remodelling. As a downstream effector of adipocytokines and cytokines, its canonical and non-canonical activities affect mitochondrial functioning and cancer metabolism. In this review, we examine the central role played by the crosstalk between the transcriptional and mitochondrial roles of STAT3 to promote survival and further oncogenesis within the tumour microenvironment with a particular focus on adipose-breast cancer interactions.

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Section: Of 24mentioning

confidence: 99%

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

Kadye

Stoffels

Fanucci

et al. 2020

Cells

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“…NAP1L3 is overexpressed in breast cancer [280]. CCH1 , which is a voltage-gated high-affinity calcium channel with several homologs that were UES, including: CACNA1A , underexpressed in breast, colorectal, esophageal, gastric, and brain cancers; CACNA1B , underexpressed in breast and brain cancers; CACNA1C , underexpressed in brain, bladder, lung, lymphoma, prostate, and renal cancers; CACNA1E , underexpressed in breast, brain, gastric, leukemia, lung, and prostate cancers; and CACNA1F , underexpressed in lymphoma [274] ; IZH1 , a yeast membrane protein involved in zinc ion homeostasis, having a human homolog, PAQR1/ADIPOR1 that encodes the adiponectin receptor protein 1, which is differentially regulated in breast cancers [278,279] ; FAT1 , a yeast fatty acid transporter and very long-chain fatty acyl-CoA synthetase that corresponds to SLC27A2 (very long-chain acyl Co-A synthetase), which is underexpressed in lung cancer [275], and SLC27A3 (long-chain fatty acid transport), which is hypermethylated in melanoma [276]; FOL2/GCH1 , a GTP-cyclohydrolase that catalyzes the first step in folic acid biosynthesis. Downregulation of GCH1 occurs in esophageal squamous cell carcinoma [277].…”

Section: Resultsmentioning

confidence: 99%

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Santos

Icyuz

Pound

et al. 2019

Preprint

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10Knowledge about synthetic lethality can be applied to enhance the efficacy of 11 anti-cancer therapies in individual patients harboring genetic alterations in their cancer 12 that specifically render it vulnerable. We investigated the potential for high-resolution 13 phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, 14 comprehensive, and quantitative assessment of drug-gene interaction for gemcitabine 15 and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures 16 yet distinct anti-tumor efficacy. Human deoxycytidine kinase (dCK) was conditionally 17 expressed in the S. cerevisiae genomic library of knockout and knockdown (YKO/KD) 18 strains, to globally and quantitatively characterize differential drug-gene interaction for 19 gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, 20 histone modification, chromatin remodeling, and apoptosis-related processes influence 21 gemcitabine specifically, while drug-gene interaction specific to cytarabine was less 22 enriched in Gene Ontology. Processes having influence over both drugs were DNA 23 repair and integrity checkpoints and vesicle transport and fusion. Non-GO-enriched 24 genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics 25 data were integrated to identify yeast-human homologs with correlated differential gene 26 2 expression and drug-efficacy, thus providing a unique resource to predict whether 27 differential gene expression observed in cancer genetic profiles are causal in tumor-28 specific responses to cytotoxic agents. 29 30 Keywords: 31 yeast phenomics, gene-drug interaction, genetic buffering, quantitative high 32 throughput cell array phenotyping (Q-HTCP), cell proliferation parameters (CPPs), 33 gemcitabine, cytarabine, recursive expectation-maximization clustering (REMc), 34 pharmacogenomics 35 36 Introduction: 37Genomics has enabled targeted therapy aimed at cancer driver genes and 38 oncogenic addiction [1], yet traditional cytotoxic chemotherapeutic agents remain among 39 the most widely used and efficacious anti-cancer therapies [2]. Changes in the genetic 40 network underlying cancer can produce vulnerabilities to cytotoxic chemotherapy that 41 further influence the therapeutic window and provide additional insight into their 42 mechanisms of action [3,4]. A potential advantage of so-called synthetic lethality-based 43 treatment strategies is that they could have efficacy against passenger gene mutation or 44 compensatory gene expression, while classic targeted therapies are directed primarily at 45 driver genes ( Fig. 1A). Quantitative high throughput cell array phenotyping of the yeast 46 knockout and knockdown libraries provides a phenomic means for systems level, high- 47resolution modeling of gene interaction [5][6][7][8][9], which is applied here to predict cancer-48 relevant drug-gene interaction through integration with cancer pharmacogenomics 49 resources ( Fig. 1B). 50Nucleoside analogs include a diverse group of co...

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“…Increased expression of leptin and its receptors was demonstrated in breast cancer cell lines and in human breast cancer tissues, since leptin and its receptors play important roles in apoptosis, cell proliferation and differentiation, mTOR (mammalian target of rapamycin) signaling, glucose regulation, inflammation, neurogenesis and gynecological diseases [3,4,[21][22][23]. Majority of the studies investigating the role of leptin and its receptors in breast cancer development were conducted with serum samples, mammary fat pad tissue or MT samples [21][22][23][24]. However, to the best of our knowledge, there is no previous study examining the association between the leptin and leptin receptor expression in liver and MT development.…”

Section: Discussionmentioning

confidence: 99%

Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

Tuna¹,

Cleary²,

Demirel³

et al. 2020

Cureus

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Leptin, an adipocytokine, is secreted from various tissues including the liver. The roles of both leptin and leptin receptor (ObR) in numerous pathophysiological conditions including mammary tumor (MT) development have been reported. However, the roles of leptin signalingrelated proteins in the liver have not been reported previously in MT development. The objective of this study was to examine the expression levels of leptin and ObR in liver tissue of a transgenic breast cancer mouse model to investigate whether the roles of leptin in MT development are systemic or local. MMTV-TGF-α transgenic female mice were fed ad-libitum from week 10 up to week 74. Protein expression levels of leptin and ObR were measured in liver tissues of 74-week-old MMTV-TGF-α mice with and without MT by western blot. Serum leptin and insulin levels were measured using a enzyme-linked immunosorbent assay. Protein expression levels of leptin and ObR were similar in mice with MT compared to the ones without MT. Serum leptin and insulin levels were also not significantly different between the two groups. These results indicate that the effects of leptin signaling in MT development might be important at a local tissue level, such as mammary fat pad, and not as important at a systemic level.

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Expression of AdipoR1 and AdipoR2 Receptors as Leptin-Breast Cancer Regulation Mechanisms

Cited by 12 publications

References 51 publications

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

Leptin Signaling in Liver Tissue of a Transgenic Breast Cancer Mouse Model

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