Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype

Thornton, Nicole; Crew, Vanja Karamatic; Tilley, Louise; Green, Carole A.; Tay, Chwen Ling; Griffiths, Rebecca E.; Singleton, Belinda K.; Spring, Frances A.; Walser, Piers J.; Alattar, Abdul Ghani; Jones, Benjamin T.; Laundy, Rosalind; Storry, Jill R.; Möller, Mattias; Wall, Lorna; Charlewood, Richard; Westhoff, Connie M.; Lomas‐Francis, Christine; Yahalom, Vered; Feick, Ute; Seltsam, Axel; Mayer, Beate; Olsson, Martin L.; Anstee, David J.

doi:10.1038/s41467-020-17060-4

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…Enucleation capacity of BEL-A was further improved by subsequent adjustment of the differentiation protocol to give a rate of $40%. 10 The unlimited proliferative window and ease of molecular manipulation, combined with unparalleled enucleation capacity, have enabled the application of BEL-A for demonstrating proof-ofprinciple production of reticulocytes with increased transfusion compatibility, 11 identifying the molecular basis of the MAM blood group antigen, 12 and the study of surface protein requirements for Plasmodium falciparum invasion. 13 However, isolation of BM CD34 + cells is highly invasive, so the ability to generate lines from more accessible PB and CB CD34 + cells is essential for opening up wider applications of the technology, such as creating lines from individuals with specific and rare blood group phenotypes and from patients with erythroid diseases for research purposes.…”

Section: Introductionmentioning

confidence: 99%

Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics

Daniels

Ferguson

Griffiths

et al. 2021

Molecular Therapy - Methods & Clinical Development

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Developing robust methodology for the sustainable production of red blood cells in vitro is essential for providing an alternative source of clinical-quality blood, particularly for individuals with rare blood group phenotypes. Immortalized erythroid progenitor cell lines are the most promising emergent technology for achieving this goal. We previously created the erythroid cell line BEL-A from bone marrow CD34 + cells that had improved differentiation and enucleation potential compared to other lines reported. In this study we show that our immortalization approach is reproducible for erythroid cells differentiated from bone marrow and also from far more accessible peripheral and cord blood CD34 + cells, consistently generating lines with similar improved erythroid performance. Extensive characterization of the lines shows them to accurately recapitulate their primary cell equivalents and provides a molecular signature for immortalization. In addition, we show that only cells at a specific stage of erythropoiesis, predominantly proerythroblasts, are amenable to immortalization. Our methodology provides a step forward in the drive for a sustainable supply of red cells for clinical use and for the generation of model cellular systems for the study of erythropoiesis in health and disease, with the added benefit of an indefinite expansion window for manipulation of molecular targets.

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Section: Introductionmentioning

confidence: 99%

Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics

Daniels

Ferguson

Griffiths

et al. 2021

Molecular Therapy - Methods & Clinical Development

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“…EMP3 belongs to the peripheral myelin protein 22 (PMP22)/claudin superfamily of proteins and has four transmembrane domains. 15 , 16 Aberrant expression of EMP3 has been found in many cancers. Recently, many studies have focused on the role of EMP3 in tumor progression and malignant transformation.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a nomogram with EMP3 for predicting clinical outcomes in patients with glioma: A bi‐center study

Zhang

et al. 2021

CNS Neurosci Ther

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“…Some previously published studies have found that PTPRC, as a kind of PTP family, could regulate the T-and B-cell antigen receptor signaling (15,16). EMP3 regulates cell growth and cell-cell interaction, and might function as a tumor suppressor in some cancers (30,31). MAPK7 as an important member of the MAPK family, and could act as a mediator for some downstream signaling pathways that are involved in a number of cellular activities, including proliferation, differentiation, transcription regulation, and development (32).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori-induced protein tyrosine phosphatase receptor type C as a prognostic biomarker for gastric cancer

Liu

et al. 2021

J Gastrointest Oncol

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Background: Helicobacter pylori (H. pylori) infection is closely associated with the tumorigenesis of gastric cancer. The aim of the present study was to identify the key regulator in H. pylori-related gastric cancer and to study the expression level and clinical value of the indicated key regulator in gastric cancer. Methods:The GSE6143 dataset was used to identify differentially expressed genes (DEGs) with limma R package, and enrichment analysis was done using the Metascape web-based portal. The protein-protein interaction analysis was done using Search Tool for the Retrieval of Interacting Genes/Proteins. Gastric adenocarcinoma AGS and BGC-823 cells were treated with H. pylori strain 26695 to construct the in vitro H. pylori infection model, and quantitative reverse transcription polymerase chain reaction was used to analyze the mRNA levels of indicated genes. The correlation analysis between two genes in gastric cancer was done by GEPIA. Furthermore, the PTPRC expression by pathological features analysis was conducted in UALCAN, an easy to use, interactive web-portal (http://ualcan.path.uab.edu). The survival analysis for gastric cancer, based on PTPRC expression levels, was done using the Kaplan-Meier plotter.Results: DEGs in gastric mucosa with or without H. pylori infection were identified and enriched in immune-related pathways and cancer pathways. The protein-protein interaction analysis confirmed the enrichment analysis of gene ontology. H. pylori strain 26695 exposure also confirmed the alteration of gene expression levels in AGS and BGC-823 cells. PTPRC was co-expressed with CSF2RB and TNFRSF7, indicating a significant positive correlation in gastric cancer. PTPRC was overexpressed in gastric cancer, and the overexpression of PTPRC was positively correlated with the progression of gastric cancer. Furthermore, the high expression of PTPRC could act as a poor prognostic factor for gastric cancer patients, especially for those at advanced stage. Conclusions: H. pylori-induced PTPRC is overexpressed in gastric cancer, and the overexpression of PTPRC is positively associated with the development of gastric cancer. The high expression of PTPRC could serve as poor prognostic biomarker for gastric cancer patients, especially for those at advanced stage. H. pylori-induced PTPRC is a prognostic biomarker for gastric cancer.

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Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype

Cited by 21 publications

References 33 publications

Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics

Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics

Establishment of a nomogram with EMP3 for predicting clinical outcomes in patients with glioma: A bi‐center study

Helicobacter pylori-induced protein tyrosine phosphatase receptor type C as a prognostic biomarker for gastric cancer

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