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In silico and in vitro mapping of receptor-type Protein Tyrosine Phosphatase Receptor Type D in health and disease : implications for asprosin signalling in endometrial cancer and neuroblastoma
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Orton, Sophie, Karkia, Rebecca, Mustafov, Denis, Gharanei, Seley, Braoudaki, Maria, Filipe, Alice, Panfilov, Suzana, Saravi, Sayeh, Khan, Nabeel, Kyrou, Ioannis, Karteris, Emmanouil, Chatterjee, Jayanta and Randeva, Harpal S. (2024) In silico and in vitro mapping of receptor-type Protein Tyrosine Phosphatase Receptor Type D in health and disease : implications for asprosin signalling in endometrial cancer and neuroblastoma. Cancers, 16 (3). p. 582. doi:10.3390/cancers16030582 ISSN 2072-6694.
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WRAP-In-silico-in-vitro-mapping-receptor-type-Protein-Tyrosine-Phosphatase-Receptor-Type-D-health-disease-2024.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (6Mb) | Preview |
Official URL: https://doi.org/10.3390/cancers16030582
Abstract
Simple Summary: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) plays a role in cell proliferation, differentiation, oncogenic transformation, and brain development and serves as an orexigenic asprosin receptor. This study investigates the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated by obesity. Using a tissue microarray, abundant PTPRD expression in low- and high-grade EC tumours is noted. Using liquid biopsies from EC patients, we show the expression of PTPRD in peripheral leukocytes. Moreover, asprosin treatment upregulates the expression of PTPRD in syncytialised placental cells in vitro, but not in EC cell lines. Collectively, our data suggest that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Abstract: Background: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). Methods: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. Results: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. Conclusions: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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SWORD Depositor: | Library Publications Router | ||||||
Journal or Publication Title: | Cancers | ||||||
Publisher: | MDPI | ||||||
ISSN: | 2072-6694 | ||||||
Official Date: | 30 January 2024 | ||||||
Dates: |
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Volume: | 16 | ||||||
Number: | 3 | ||||||
Page Range: | p. 582 | ||||||
DOI: | 10.3390/cancers16030582 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 14 March 2024 | ||||||
Date of first compliant Open Access: | 14 March 2024 |
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