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  • 1
    Language: English
    In: The Journal of clinical investigation, 2017-08-01, Vol.127 (8), p.3075-3089
    Description: Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance. Mechanistically, the formation of a protein complex comprising NEK2 and EZH2 in glioma spheres phosphorylated and then protected EZH2 from ubiquitination-dependent protein degradation in a NEK2 kinase activity-dependent manner. Clinically, NEK2 expression in patients with glioma was closely associated with EZH2 expression and correlated with a poor prognosis. NEK2 expression was also substantially elevated in recurrent tumors after therapeutic failure compared with primary untreated tumors in matched GBM patients. We designed a NEK2 kinase inhibitor, compound 3a (CMP3a), which efficiently attenuated GBM growth in a mouse model and exhibited a synergistic effect with radiotherapy. These data demonstrate a key role for NEK2 in maintaining GSCs in GBM by stabilizing the EZH2 protein and introduce the small-molecule inhibitor CMP3a as a potential therapeutic agent for GBM.
    Subject(s): Neoplasm Transplantation ; Enhancer of Zeste Homolog 2 Protein - metabolism ; Phosphorylation ; Humans ; Gene Silencing ; Brain Neoplasms - drug therapy ; Glioblastoma - radiotherapy ; Animals ; Neoplastic Stem Cells - metabolism ; Mice, Nude ; NIMA-Related Kinases - antagonists & inhibitors ; NIMA-Related Kinases - chemistry ; Female ; Antineoplastic Agents - pharmacology ; Mice ; Brain Neoplasms - radiotherapy ; Glioblastoma - drug therapy ; Care and treatment ; Usage ; Methyltransferases ; Research ; Diagnosis ; Radiotherapy ; Binding proteins ; Glioblastoma multiforme ; Brain tumors ; Brain cancer ; Glioblastoma ; Stem cell transplantation ; Radioresistance ; Breast cancer ; Spheres ; Radiation therapy ; Kinases ; Cancer therapies ; Patients ; Ovarian cancer ; Proteins ; Studies ; Ubiquitination ; Chemotherapy ; Allografts ; Glioma cells ; Medical prognosis ; Stem cells ; Cell cycle ; Histone methyltransferase ; Tumors
    ISSN: 0021-9738
    E-ISSN: 1558-8238
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Brain pathology (Zurich, Switzerland), 2013-01, Vol.23 (1), p.60-72
    Description: In various types of cancers including glioblastoma, accumulating evidence show the existence of cancer stem‐like cells (CSCs), characterized by stem cell marker expression, capability of differentiation and self‐renewal, and high potential for tumor propagation in vivo. LGR5, whose expression is positively regulated by the Wnt signaling pathway, is a stem cell marker in intestinal mucosa and hair follicle in the skin. As Wnt signaling is also involved in brain development, the function of LGR5 in the maintenance of brain CSCs is to be assessed. Our study showed that the LGR5 transcript level was increased in CSCs. Co‐immunofluorescence staining demonstrated the co‐localization of CD133‐ and LGR5‐positive cells in glioblastoma tissue sections. Functionally, silencing of LGR5 by lentiviral shRNA‐mediated knockdown induced apoptosis in brain CSCs. Moreover, LGR5 depletion led to a downregulation of L1 cell adhesion molecule expression. In line with an important function in glioma tumorigenesis, LGR5 expression increased with glioma progression and correlated with an adverse outcome. Our findings suggest that LGR5 plays a role in maintenance and/or survival of brain CSCs.
    Subject(s): apoptosis ; glioma ; glioblastoma ; cancer stem cell ; LGR5 ; RNA, Small Interfering - genetics ; Prognosis ; Receptors, G-Protein-Coupled - metabolism ; Tissue Array Analysis ; Humans ; Neural Cell Adhesion Molecule L1 - genetics ; Brain Neoplasms - pathology ; Gene Expression Regulation, Neoplastic ; Glycoproteins - metabolism ; Statistics as Topic ; Antigens, CD - metabolism ; Cell Differentiation - genetics ; Peptides - metabolism ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Lentivirus - genetics ; Neural Cell Adhesion Molecule L1 - metabolism ; Glioblastoma - diagnosis ; Cell Survival ; Brain Neoplasms - diagnosis ; Cells, Cultured ; AC133 Antigen ; Glioblastoma - pathology ; Genetic Vectors - physiology ; Apoptosis ; RNA, Small Interfering - metabolism ; Development and progression ; Glioblastoma multiforme ; Brain tumors ; Stem cells ; Cancer ; Index Medicus
    ISSN: 1015-6305
    E-ISSN: 1750-3639
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: International journal of cancer, 2016-10-15, Vol.139 (8), p.1776-1787
    Description: In a previous study, Protein Kinase C iota (PRKCI) emerged as an important candidate gene for glioblastoma (GBM) stem‐like cell (GSC) survival. Here, we show that PKCι is overexpressed and activated in patient derived GSCs compared with normal neural stem cells and normal brain lysate, and that silencing of PRKCI in GSCs causes apoptosis, along with loss of clonogenicity and reduced proliferation. Notably, PRKCI silencing reduces tumor growth in vivo in a xenograft mouse model. PKCι has been intensively studied as a therapeutic target in non‐small cell lung cancer, resulting in the identification of an inhibitor, aurothiomalate (ATM), which disrupts the PKCι/ERK signaling axis. However, we show that, although sensitive to pharmacological inhibition via a pseudosubstrate peptide inhibitor, GSCs are much less sensitive to ATM, suggesting that PKCι acts along a different signaling axis in GSCs. Gene expression profiling of PRKCI‐silenced GSCs revealed a novel role of the Notch signaling pathway in PKCι mediated GSC survival. A proximity ligation assay showed that Notch1 and PKCι are in close proximity in GSCs. Targeting PKCι in the context of Notch signaling could be an effective way of attacking the GSC population in GBM. What's new? Increased understanding of gene expression patterns in glioblastoma (GBM) has led to the identification of genes involved in survival, among them protein kinase C iota (PRKCI). PRKCI is classified as an oncogene in several human cancer types. In this study, PRKCI was found to be overexpressed in patient‐derived GBM stem‐like cells (GSCs) and to play a crucial role in GSC survival through Notch signaling. Its silencing slowed tumor growth and prolonged survival in a xenograft GBM mouse model. The findings highlight the therapeutic promise of PKCι and its potential to provide a new avenue for GSC‐targeted GBM therapies.
    Subject(s): atypical protein kinase C iota ; glioblastoma ; notch signaling ; glioblastoma stem‐like cells ; Protein Kinase C - genetics ; Glioblastoma - enzymology ; Neoplastic Stem Cells - drug effects ; Receptors, Notch - metabolism ; Humans ; Brain Neoplasms - pathology ; Apoptosis - genetics ; Gene Expression Profiling ; Molecular Targeted Therapy ; Glioblastoma - genetics ; Isoenzymes - metabolism ; Protein Kinase C - metabolism ; HEK293 Cells ; Neoplastic Stem Cells - pathology ; Brain Neoplasms - enzymology ; Isoenzymes - genetics ; Gene Silencing ; Neural Stem Cells - drug effects ; Brain Neoplasms - genetics ; Protein Kinase C - antagonists & inhibitors ; Brain Neoplasms - drug therapy ; Mice, SCID ; Neural Stem Cells - enzymology ; Neural Stem Cells - pathology ; Animals ; Glioblastoma - pathology ; Protein Kinase C - biosynthesis ; Mice, Inbred NOD ; Mice ; Protein Kinase Inhibitors - pharmacology ; Enzyme Activation ; Glioblastoma - drug therapy ; Isoenzymes - biosynthesis ; Neoplastic Stem Cells - enzymology ; Isoenzymes - antagonists & inhibitors ; Analysis ; Stem cells ; Automated teller machines ; Lung cancer, Non-small cell ; Gene expression ; Glioblastoma multiforme ; Protein kinases ; Index Medicus
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: The Journal of pathology, 2014-09, Vol.234 (1), p.23-33
    Description: Cancer cells with enhanced self‐renewal capacity influence tumour growth in glioblastoma. So far, a variety of surrogate markers have been proposed to enrich these cells, emphasizing the need to devise new characterization methods. Here, we screen a large panel of glioblastoma cultures (n = 21) cultivated under stem cell‐permissive conditions and identify several cell lines with enhanced self‐renewal capacity. These cell lines are capable of matrix‐independent growth and form fast‐growing, orthotopic tumours in mice. Employing isolation, re‐plating, and label‐retention techniques, we show that self‐renewal potential of individual cells is partitioned asymmetrically between daughter cells in a robust and cell line‐specific fashion. This yields populations of fast‐ and slow‐cycling cells, which differ in the expression of cell cycle‐associated transcripts. Intriguingly, fast‐growing cells keep their slow‐cycling counterparts in a reversible state of quiescence associated with high chemoresistance. Our results suggest that two different subpopulations of tumour cells contribute to aberrant growth and tumour recurrence after therapy in glioblastoma. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Subject(s): self‐renewal; glioblastoma; label retention; quiescence ; Gene Dosage - genetics ; Cell Proliferation ; Oligonucleotide Array Sequence Analysis ; Humans ; Brain Neoplasms - pathology ; Gene Expression Profiling ; Brain Neoplasms - metabolism ; Neoplasm Recurrence, Local - pathology ; Animals ; Comparative Genomic Hybridization ; Neoplastic Stem Cells - metabolism ; Glioblastoma - pathology ; Cell Line, Tumor ; Neoplastic Stem Cells - pathology ; Glioblastoma - metabolism ; Mice ; Disease Models, Animal ; Glioblastoma multiforme ; Analysis ; Stem cells ; Index Medicus
    ISSN: 0022-3417
    E-ISSN: 1096-9896
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Cancer management and research, 2014, Vol.6 (default), p.171-180
    Description: The concept of cancer stem cells has gained considerable interest in the last few decades, partly because of their potential implication in therapy resistance. However, the lack of specific cellular surface markers for these cells has impeded their isolation, making the characterization of this cellular subpopulation technically challenging. Recent studies have indicated that leucine-rich repeat-containing G-protein-coupled receptor 4 and 5 (LGR4 and LGR5) expression in multiple organs may represent a global marker of adult stem cells. This review aims to give an overview of LGR4 and LGR5 as cancer stem cell markers and their function in development.
    Subject(s): Cell receptors ; Cancer cells ; Stem cells ; Genetic aspects ; Properties ; Carcinogenesis ; Health aspects ; Medical research ; Enzymes ; Phosphorylation ; Transplants & implants ; Research & development--R&D ; Leukemia ; Genes ; Colorectal cancer ; Kinases ; Cell adhesion & migration ; Proteins ; Epigenetics ; Population ; Ligands ; Tumorigenesis ; Mutation ; Stochastic models ; Tumors ; glioblastoma ; colorectal cancer ; tissue stem cell marker ; Review
    ISSN: 1179-1322
    E-ISSN: 1179-1322
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: EMBO molecular medicine, 2012-01, Vol.4 (1), p.38-51
    Description: Malignant astrocytomas are highly aggressive brain tumours with poor prognosis. While a number of structural genomic changes and dysregulation of signalling pathways in gliomas have been described, the identification of biomarkers and druggable targets remains an important task for novel diagnostic and therapeutic approaches. Here, we show that the Wnt‐specific secretory protein Evi (also known as GPR177/Wntless/Sprinter) is overexpressed in astrocytic gliomas. Evi/Wls is a core Wnt signalling component and a specific regulator of pan‐Wnt protein secretion, affecting both canonical and non‐canonical signalling. We demonstrate that its depletion in glioma and glioma‐derived stem‐like cells led to decreased cell proliferation and apoptosis. Furthermore, Evi/Wls silencing in glioma cells reduced cell migration and the capacity to form tumours in vivo. We further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling. Taken together, our study identifies Evi/Wls as an essential regulator of glioma tumourigenesis, identifying a pathway‐specific protein trafficking factor as an oncogene and offering novel therapeutic options to interfere with the aberrant regulation of growth factors at the site of production.
    Subject(s): glioma ; RNAi ; Wnt secretion ; Wnt signalling ; cancer research ; Receptors, G-Protein-Coupled - metabolism ; Humans ; Brain Neoplasms - pathology ; Transcriptome ; Transplantation, Heterologous ; Intracellular Signaling Peptides and Proteins - metabolism ; Wnt Proteins - metabolism ; Brain Neoplasms - metabolism ; Interleukins - metabolism ; Glioma - metabolism ; RNA Interference ; Cell Transformation, Neoplastic - genetics ; Glioma - pathology ; Intracellular Signaling Peptides and Proteins - genetics ; Signal Transduction ; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors ; Cell Transformation, Neoplastic - metabolism ; Cell Cycle Checkpoints ; Animals ; Mice, Nude ; Receptors, G-Protein-Coupled - antagonists & inhibitors ; Cell Line, Tumor ; Mice ; Receptors, G-Protein-Coupled - genetics ; Apoptosis ; Cell Movement ; RNA, Small Interfering - metabolism ; Molecular genetics ; Gliomas ; Oncology, Experimental ; Brain tumors ; Research ; Universities and colleges ; College teachers ; Cells ; Cancer ; Cell proliferation ; Wnt protein ; Pathogenesis ; Secretion ; Brain cancer ; Genomics ; Gene expression ; Kinases ; Experiments ; Proteins ; Signal transduction ; Brain research ; Medical prognosis ; Glioma cells ; Cell cycle ; Ligands ; Tumorigenesis ; Mutation ; Protein transport ; Growth factors ; Cell migration ; Tumors ; Index Medicus
    ISSN: 1757-4676
    E-ISSN: 1757-4684
    Source: HighWire Press (Free Journals)
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Stem cell reports, 2015-05-12, Vol.4 (5), p.899-913
    Description: Glioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs) were recently identified: mesenchymal (MES) and proneural (PN). To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis and kinome-wide short hairpin RNA screening of MES and PN GSCs. In comparison to PN GSCs, we found significant upregulation and phosphorylation of the receptor tyrosine kinase AXL in MES GSCs. Knockdown of AXL significantly decreased MES GSC self-renewal capacity in vitro and inhibited the growth of glioblastoma patient-derived xenografts. Moreover, inhibition of AXL with shRNA or pharmacologic inhibitors also increased cell death significantly more in MES GSCs. Clinically, AXL expression was elevated in the MES GBM subtype and significantly correlated with poor prognosis in multiple cancers. In conclusion, we identified AXL as a potential molecular target for novel approaches to treat glioblastoma and other solid cancers. •shRNA screen identified kinases that alter GSC viability in a subtype-dependent manner•AXL is highly expressed in mesenchymal GSCs•Targeting AXL decreases mesenchymal GSC self-renewal, viability, and tumorigenicity•AXL expression predicts poor prognosis in several tumor types To identify mechanistic differences between the mesenchymal and proneural glioblastoma subtypes, Goidts, Nakano, and colleagues performed a phenotypic screen, silencing the whole kinome in patient-derived mesenchymal and proneural glioblastoma stem-like cells (GSCs). AXL was identified as an important regulator of mesenchymal GSC viability and tumorigenicity, making it an attractive therapeutic target.
    Subject(s): Immunohistochemistry ; Up-Regulation ; Neoplastic Stem Cells - cytology ; Phosphorylation ; Cell Proliferation ; Humans ; Brain Neoplasms - pathology ; Transplantation, Heterologous ; Carcinogenesis ; Glioblastoma - genetics ; Neoplastic Stem Cells - metabolism ; RNA Interference ; Hyaluronan Receptors - metabolism ; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors ; Brain Neoplasms - mortality ; Tumor Cells, Cultured ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins - antagonists & inhibitors ; Kaplan-Meier Estimate ; Brain Neoplasms - genetics ; Proto-Oncogene Proteins - genetics ; Mice, SCID ; Receptor Protein-Tyrosine Kinases - metabolism ; Animals ; Receptor Protein-Tyrosine Kinases - genetics ; Glioblastoma - pathology ; Mice, Inbred NOD ; Mice ; Neoplasm Staging ; Glioblastoma - mortality ; Apoptosis ; RNA, Small Interfering - metabolism ; Index Medicus
    ISSN: 2213-6711
    E-ISSN: 2213-6711
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Marine drugs, 2017-08-13, Vol.15 (8), p.253
    Description: A marine-derived fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated.
    Subject(s): Marine Biology ; Biological Products - chemistry ; Chromatography, High Pressure Liquid - methods ; Diterpenes - isolation & purification ; Antifungal Agents - chemistry ; Molecular Structure ; Hypocreales - chemistry ; Chromatography, Liquid - methods ; Mass Spectrometry - methods ; Biological Products - isolation & purification ; Diterpenes - chemistry ; Index Medicus ; antifungal ; HRMS ; ilicicolin H ; marine-derived ; pimarane-type diterpenoids ; dereplication ; bioguided-discovery ; cytotoxicity ; MS/HRMS
    ISSN: 1660-3397
    E-ISSN: 1660-3397
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Glia, 2015-10, Vol.63 (10), p.1850-1859
    Description: Objectives Measuring concentrations of the differentiation‐promoting hormone retinoic acid (RA) in glioblastoma tissues would help to understand the reason why RA treatment has been inefficient in clinical trials involving brain tumor patients. Here, we apply a recently established extraction and measurement protocol to screen glioblastoma tissues for the levels of the RA precursor retinol and biologically active RA. Combining this approach with mRNA analyses of 26 tumors and 8 normal brains, we identify a multifaceted disturbance of RA synthesis in glioblastoma, involving multiple aldehyde dehydrogenase 1 family and retinol dehydrogenase enzymes. Through database studies and methylation analyses, we narrow down chromosomal deletions and aberrant promoter hypermethylation as potential mechanisms accounting for these alterations. Employing chromatin immunoprecipitation analyses and cell‐culture studies, we further show that chromatin at RA target genes is poised to RA substitution, but most glioblastoma cell cultures are completely resistant to RA treatment. This paradoxical RA response is unrelated to alternative RA signaling through the fatty acid‐binding protein 5/peroxisome proliferator‐activated receptor delta axis. Our data suggest a multifaceted disturbance of RA synthesis in glioblastoma and contribute to reconsider current RA treatment strategies. GLIA 2015;63:1850–1859 Main Points Retinoic acid synthesis is impaired in glioblastoma. Most glioblastoma cultures are resistant to retinoic acid. Current retinoic acid treatment strategies in glioblastoma need to account for retinoid resistance in tumor cells.
    Subject(s): glioma ; retinoic acid ; differentiation ; Humans ; Retinal Dehydrogenase - metabolism ; Enzyme Inhibitors - pharmacology ; Receptors, Retinoic Acid - metabolism ; Retinol O-Fatty-Acyltransferase - metabolism ; Brain Neoplasms - complications ; Receptors, Retinoic Acid - genetics ; Brain - drug effects ; Brain - metabolism ; DNA Methylation ; Databases, Bibliographic - statistics & numerical data ; Chromatin Immunoprecipitation ; Signal Transduction - drug effects ; Tretinoin - metabolism ; Isoenzymes - metabolism ; Glioblastoma - complications ; Cell Proliferation - drug effects ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - physiology ; Retinoids - pharmacology ; Enzymes ; RNA ; Analysis ; Methylation ; Aldehydes ; Fatty acids ; Glioblastoma multiforme ; Protein binding ; Tretinoin ; Index Medicus
    ISSN: 0894-1491
    E-ISSN: 1098-1136
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Oncogenesis (New York, NY), 2020-02-13, Vol.9 (2), p.18-18
    Description: PKR-like kinase (PERK) plays a significant role in inducing angiogenesis in various cancer types including glioblastoma. By proteomics analysis of the conditioned medium from a glioblastoma cell line treated with a PERK inhibitor, we showed that peptidylglycine α-amidating monooxygenase (PAM) expression is regulated by PERK under hypoxic conditions. Moreover, PERK activation via CCT020312 (a PERK selective activator) increased the cleavage and thus the generation of PAM cleaved cytosolic domain (PAM sfCD) that acts as a signaling molecule from the cytoplasm to the nuclei. PERK was also found to interact with PAM, suggesting a possible involvement in the generation of PAM sfCD. Knockdown of PERK or PAM reduced the formation of tubes by HUVECs in vitro. Furthermore, in vivo data highlighted the importance of PAM in the growth of glioblastoma with reduction of PAM expression in engrafted tumor significantly increasing the survival in mice. In summary, our data revealed PAM as a potential target for antiangiogenic therapy in glioblastoma.
    Subject(s): Angiogenesis ; Hypoxia ; Monooxygenase ; Cytoplasm ; Glioblastoma ; Proteomics
    ISSN: 2157-9024
    E-ISSN: 2157-9024
    Source: Nature Open Access
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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