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EPHA2

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https://www.readbyqxmd.com/read/28911167/in-utero-exposure-to-a-high-fat-diet-programs-hepatic-hypermethylation-and-gene-dysregulation-and-development-of-metabolic-syndrome-in-male-mice
#1
Yoshinori Seki, Masako Suzuki, Xingyi Guo, Alan Scott Glenn, Patricia M Vuguin, Ariana Fiallo, Quan Du, Yi-An Ko, Yiting Yu, Katalin Susztak, Deyou Zheng, John M Greally, Ellen B Katz, Maureen J Charron
Exposure to a high-fat (HF) diet in utero is associated with increased incidence of cardiovascular disease, diabetes, and metabolic syndrome later in life. However, the molecular basis of this enhanced susceptibility for metabolic disease is poorly understood. Gene expression microarray and genome-wide DNA methylation analyses of mouse liver revealed that exposure to a maternal HF milieu activated genes of immune response, inflammation, and hepatic dysfunction. DNA methylation analysis revealed 3360 differentially methylated loci, most of which (76%) were hypermethylated and distributed preferentially to hotspots on chromosomes 4 [atherosclerosis susceptibility quantitative trait loci (QTLs) 1] and 18 (insulin-dependent susceptibility QTLs 21)...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28883622/socs2-binds-to-and-regulates-epha2-through-multiple-mechanisms
#2
Carissa Pilling, Jonathan A Cooper
Suppressors of cytokine signaling (SOCS) proteins inhibit signaling by serving as substrate receptors for the Cullin5-RING E3 ubiquitin ligase (CRL5) and through a variety of CRL5-independent mechanisms. CRL5, SOCS2 and SOCS6 are implicated in suppressing transformation of epithelial cells. We identified cell proteins that interact with SOCS2 and SOCS6 using two parallel proteomics techniques: BioID and Flag affinity purification mass spectrometry. The receptor tyrosine kinase ephrin type-A receptor 2 (EphA2) was identified as a SOCS2-interacting protein...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881807/associations-of-high-altitude-polycythemia-with-polymorphisms-in-epha2-and-agt-in-chinese-han-and-tibetan-populations
#3
Lijun Liu, Yao Zhang, Zhiying Zhang, Yiduo Zhao, Xiaowei Fan, Lifeng Ma, Yuan Zhang, Haijin He, Longli Kang
High altitude polycythemia (HAPC) refers to the long-term living in the plateau of the hypoxia environment is not accustomed to cause red blood cell hyperplasia. The pathological changes are mainly the various organs and tissue congestion, blood stasis and hypoxia damage. Although chronic hypoxia is the main cause of HAPC, the related molecular mechanisms remain largely unclear. This study aims to explore the genetic basis of HAPC in the Chinese Han and Tibetan populations. We enrolled 100 patients (70 Han, 30 Tibetan) with HAPC and 100 healthy control subjects (30 Han, 70 Tibetan)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28855599/functional-non-coding-polymorphism-in-an-epha2-promoter-pax2-binding-site-modifies-expression-and-alters-the-mapk-and-akt-pathways
#4
Xiaoyin Ma, Zhiwei Ma, Xiaodong Jiao, J Fielding Hejtmancik
To identify possible genetic variants influencing expression of EPHA2 (Ephrin-receptor Type-A2), a tyrosine kinase receptor that has been shown to be important for lens development and to contribute to both congenital and age related cataract when mutated, the extended promoter region of EPHA2 was screened for variants. SNP rs6603883 lies in a PAX2 binding site in the EPHA2 promoter region. The C (minor) allele decreased EPHA2 transcriptional activity relative to the T allele by reducing the binding affinity of PAX2...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851287/epha-receptors-and-ephrin-a-ligands-are-upregulated-by-monocytic-differentiation-maturation-and-promote-cell-adhesion-and-protrusion-formation-in-hl60-monocytes
#5
Midori Mukai, Norihiko Suruga, Noritaka Saeki, Kazushige Ogawa
BACKGROUND: Eph signaling is known to induce contrasting cell behaviors such as promoting and inhibiting cell adhesion/spreading by altering F-actin organization and influencing integrin activities. We have previously demonstrated that EphA2 stimulation by ephrin-A1 promotes cell adhesion through interaction with integrins and integrin ligands in two monocyte/macrophage cell lines. Although mature mononuclear leukocytes express several members of the EphA/ephrin-A subclass, their expression has not been examined in monocytes undergoing during differentiation and maturation...
August 29, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28835699/differential-responsiveness-of-met-inhibition-in-non-small-cell-lung-cancer-with-altered-cbl
#6
Yi-Hung Carol Tan, Tamara Mirzapoiazova, Brian M Won, Li Zhu, Minu K Srivastava, Everett E Vokes, Aliya N Husain, Surinder K Batra, Sherven Sharma, Ravi Salgia
Casitas B-lineage lymphoma (CBL) is an E3 ubiquitin ligase and a molecule of adaptor that we have shown is important for non-small-cell lung cancer (NSCLC). We investigated if MET is a target of CBL and if enhanced in CBL-altered NSCLC. We showed that CBL wildtype cells have lower MET expression than CBL mutant cells. Ubiquitination of MET was also decreased in CBL mutant cells compared to wildtype cells. Mutant cells were also more sensitive to MET inhibitor SU11274 than wild-type cells. sh-RNA-mediated knockdown of CBL enhanced cell motility and colony formation in NSCLC cells, and these activities were inhibited by SU11274...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28833247/effect-of-dasatinib-in-a-xenograft-mouse-model-of-canine-histiocytic-sarcoma-and-in-vitro-expression-status-of-its-potential-target-epha2
#7
K Ito, R Miyamoto, H Tani, S Kurita, M Kobayashi, K Tamura, M Bonkobara
Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues...
August 17, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28804547/epha2-targeted-intratumoral-therapy-for-non-small-cell-lung-cancer-using-albumin-mesospheres
#8
Hung-Yen Lee, Kamal A Mohammed, Fredric Kaye, Brij M Moudgil, Najmunnisa Nasreen
Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer mortality and the prognosis of patients with advanced or metastatic NSCLC is poor. Despite significant advances in diagnosis and treatment, little improvement has been seen in NSCLC mortality. Recently, Intratumoral Chemotherapy, a direct local delivery of chemotherapeutic drugs, has shown promise in clinical studies. However, toxicity and high dosage of chemotherapeutic agents used for treatment are a limitation. Moreover, these drugs damage indiscriminately, cancerous as well as normal tissues...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28791195/nanoplasmonic-quantification-of-tumor-derived-extracellular-vesicles-in-plasma-microsamples-for-diagnosis-and-treatment-monitoring
#9
Kai Liang, Fei Liu, Jia Fan, Dali Sun, Chang Liu, Christopher J Lyon, David W Bernard, Yan Li, Kenji Yokoi, Matthew H Katz, Eugene J Koay, Zhen Zhao, Ye Hu
Tumour-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays require large samples, are time-consuming, low-throughput and costly, and thus impractical for clinical use. Here, we describe a rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumor-derived EVs from as little as 1 μL of plasma. The assay uses the binding of antibody-conjugated gold nanospheres and nanorods to EVs captured by EV-specific antibodies on a sensor chip to produce a local plasmon effect that enhances tumour-derived EV detection sensitivity and specificity...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28775148/the-tumor-suppressor-protein-opcml-potentiates-anti-egfr-and-anti-her2-targeted-therapy-in-her2-positive-ovarian-and-breast-cancer
#10
Elisa Zanini, Louay S Louis, Jane Antony, Evdoxia Karali, Imoh S Okon, Arthur B McKie, Sebastian Vaughan, Mona El-Bahrawy, Justin Stebbing, Chiara Recchi, Hani Gabra
OPCML is a tumor suppressor gene that is frequently inactivated in ovarian cancer and many other cancers by somatic methylation. We have previously shown that OPCML exerts its suppressor function by negatively regulating a spectrum of receptor tyrosine kinases (RTKs), such as ErbB2/HER2, FGFR1 and EphA2, thus attenuating their related downstream signaling. The physical interaction of OPCML with this defined group of RTKs is a prerequisite for their downregulation. Overexpression/gene amplification of EGFR and HER2 is a frequent event in multiple cancers including ovarian and breast cancers...
August 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28746857/enhancing-irreversible-electroporation-by-manipulating-cellular-biophysics-with-a-molecular-adjuvant
#11
Jill W Ivey, Eduardo L Latouche, Megan L Richards, Glenn J Lesser, Waldemar Debinski, Rafael V Davalos, Scott S Verbridge
Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration...
July 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28743499/all-trans-retinoic-acid-attenuates-bleomycin-induced-pulmonary-fibrosis-via-downregulating-epha2-ephrina1-signaling
#12
Ah Young Leem, Mi Hwa Shin, Ivor S Douglas, Joo Han Song, Kyung Soo Chung, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Joon Chang, Young Sam Kim, Moo Suk Park
The role of all-trans retinoic acid (ATRA) in pulmonary fibrosis is relatively unknown, although this metabolite modulates cell differentiation, proliferation, and development. We aimed to evaluate the role of ATRA in bleomycin-induced pulmonary fibrosis, and whether the mechanism involves EphA2-EphrinA1 and PI3K-Akt signaling. We evaluated three groups of mice: a control group (intraperitoneal DMSO injection 3 times weekly after PBS instillation), bleomycin group (intraperitoneal DMSO injection 3 times weekly after bleomycin instillation), and bleomycin + ATRA group (intraperitoneal ATRA injection 3 times weekly after bleomycin instillation)...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28740575/identification-of-novel-diagnostic-and-prognostic-mirna-signatures-in-endometrial-cancer
#13
Muralidharan Jayaraman, Rangasudhagar Radhakrishnan, Cara A Mathews, Mingda Yan, Sanam Husain, Katherine M Moxley, Yong Sang Song, Danny N Dhanasekaran
With the goal of identifying diagnostic and prognostic biomarkers in endometrial cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84-cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96-5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR-374a and let-7 family of miRNAs in endometrial cancer. We validated the dysregulated expression of the identified miRNAs in a panel of endometrial cancer cell-lines...
May 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28705041/ionizing-radiation-induces-epha2-s897-phosphorylation-in-a-mek-erk-rsk-dependent-manner
#14
Paul R Graves, Shaun U Din, Mark Ashamalla, Hani Ashamalla, Thomas S K Gilbert, Lee M Graves
PURPOSE: The EphA2 tyrosine kinase is frequently overexpressed in human tumors that are also treated with radiation. However, few studies have examined the effect of radiation on the EphA2 receptor itself. The purpose of this project was to investigate the impact of radiation on EphA2 to better understand mechanisms of radioresistance. MATERIALS AND METHODS: Cell lines were exposed to X-rays and assayed for changes in EphA2 protein levels and phosphorylation over time by Western blotting...
July 14, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28686661/engineering-of-monobody-conjugates-for-human-epha2-specific-optical-imaging
#15
Min-A Kim, Hee Seung Yoon, Seung-Hwan Park, Dong-Yeon Kim, Ayoung Pyo, Hyeon Sik Kim, Jung-Joon Min, Yeongjin Hong
In a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E. coli. E1-Rluc8 and E1-EGFP specifically bound to hEphA2 in human prostate cancer PC3 cells but not in human cervical cancer HeLa cells, which express hEphA2 at high and low levels, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28674216/microrna-200c-increases-radiosensitivity-of-human-cancer-cells-with-activated-egfr-associated-signaling
#16
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H Kim, David J Lee, In Ah Kim
MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c...
July 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28648759/epha2-and-ephrin-a5-are-not-a-receptor-ligand-pair-in-the-ocular-lens
#17
Catherine Cheng, Velia M Fowler, Xiaohua Gong
Eph-ephrin bidirectional signaling is essential for eye lens transparency in humans and mice. Our previous studies in mouse lenses demonstrate that ephrin-A5 is mainly expressed in the anterior epithelium, where it is required for maintaining the anterior epithelial monolayer. In contrast, EphA2 is localized in equatorial epithelial and fiber cells where it is essential for equatorial epithelial and fiber cell organization and hexagonal cell shape. Immunostaining of lens epithelial and fiber cells reveals that EphA2 and ephrin-A5 are also co-expressed in anterior fiber cell tips, equatorial epithelial cells and newly formed lens fibers, although they are not precisely colocalized...
September 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28637002/associations-of-high-altitude-polycythemia-with-polymorphisms-in-epha2-and-agt-in-chinese-han-and-tibetan-populations
#18
Lijun Liu, Yao Zhang, Zhiying Zhang, Yiduo Zhao, Xiaowei Fan, Lifeng Ma, Yuan Zhang, Haijin He, Longli Kang
High altitude polycythemia (HAPC) refers to the long-term living in the plateau of the hypoxia environment is not accustomed to cause red blood cell hyperplasia. The pathological changes are mainly the various organs and tissue congestion, blood stasis and hypoxia damage. Although chronic hypoxia is the main cause of HAPC, the related molecular mechanisms remain largely unclear. This study aims to explore the genetic basis of HAPC in the Chinese Han and Tibetan populations. We enrolled 100 patients (70 Han, 30 Tibetan) with HAPC and 100 healthy control subjects (30 Han, 70 Tibetan)...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636467/normal-epithelial-cells-trigger-epha2-dependent-rasv12-cell-repulsion-at-the-single-cell-level
#19
William Hill, Catherine Hogan
Epithelial cells expressing oncogenic Ras (RasV12) are detected by normal neighbors and are often extruded from tissues. We recently demonstrated that differential EphA2 signaling drives the segregation of mutant cells from normal monolayers via cell repulsion and increased RasV12 cell contractility. EphA2 signaling on RasV12 cells is triggered by ephrin-A ligands presented by normal cells. Here, we show that normal epithelial cells trigger the repulsion and enhanced contractility of Ras-transformed epithelial cells at the single cell level...
June 21, 2017: Small GTPases
https://www.readbyqxmd.com/read/28631589/comparison-of-protein-expression-during-wild-type-and-e1b-55k-deletion-adenovirus-infection-using-quantitative-time-course-proteomics
#20
Yen Rong Fu, Andrew S Turnell, Simon Davis, Kate J Heesom, Vanessa C Evans, David A Matthews
Adenovirus has evolved strategies to usurp host-cell factors and machinery to facilitate its life cycle, including cell entry, replication, assembly and egress. Adenovirus continues, therefore, to be an important model system for investigating fundamental cellular processes. The role of adenovirus E1B-55k in targeting host-cell proteins that possess antiviral activity for proteasomal degradation is now well established. To expand our understanding of E1B-55k in regulating the levels of host-cell proteins, we performed comparative proteome analysis of wild-type, and E1B-55k-deletion, adenovirus-infected cancer cells...
June 2017: Journal of General Virology
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