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EPHA2

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https://www.readbyqxmd.com/read/28705041/ionizing-radiation-induces-epha2-s897-phosphorylation-in-a-mek-erk-rsk-dependent-manner
#1
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
#2
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
#3
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
#4
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...
June 23, 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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28624791/epha2-affects-the-sensitivity-of-oxaliplatin-by-inducing-emt-in-oxaliplatin-resistant-gastric-cancer-cells
#8
Qiaocheng Wen, Zihua Chen, Zhikang Chen, Jinxiang Chen, Ran Wang, Changhao Huang, Weijie Yuan
Erythropoietin-producing hepatocellular receptor A2 (EphA2) is upregulated in gastric cancer tissues and cells, which is accompanied by epithelial-mesenchymal transition (EMT). The current study was designed to establish the oxaliplatin-resistant human gastric cancer cell line SGC-7901/L-OHP, to determine if EMT in these cells could be reversed, and to determine if the susceptibility of these cells to oxaliplatin was affected by silencing EphA2 expression. We found that EphA2 expression levels were upregulated in gastric cancer and associated with chemotherapy sensitivity...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28602916/structural-investigation-of-a-c-terminal-epha2-receptor-mutant-does-mutation-affect-the-structure-and-interaction-properties-of-the-sam-domain
#9
Flavia A Mercurio, Susan Costantini, Concetta Di Natale, Luciano Pirone, Stefano Guariniello, Pasqualina L Scognamiglio, Daniela Marasco, Emilia M Pedone, Marilisa Leone
Ephrin A2 receptor (EphA2) plays a key role in cancer, it is up-regulated in several types of tumors and the process of ligand-induced receptor endocytosis, followed by degradation, is considered as a potential path to diminish tumor malignancy. Protein modulators of this mechanism are recruited at the cytosolic Sterile alpha motif (Sam) domain of EphA2 (EphA2-Sam) through heterotypic Sam-Sam associations. These interactions engage the C-terminal helix of EphA2 and close loop regions (the so called End Helix side)...
June 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28590061/porphyromonas-gingivalis-lipopolysaccharide-regulates-ephrin-eph-signalling-in-human-periodontal-ligament-fibroblasts
#10
M Li, C Zhang, L Jin, K Matsuo, Y Yang
OBJECTIVE: EphrinA2-EphA2 and ephrinB2-EphB4 critically engage in bidirectional signalling to modulate alveolar bone remodelling. The present study aimed to investigate the effects of lipopolysaccharides (LPS) derived from Porphyromonas gingivalis on ephrin/Eph signalling in periodontal ligament fibroblasts (PDLFs). MATERIAL AND METHODS: The primary cultured PDLFs were incubated in the absence (as a control) or presence of P. gingivalisLPS at 0.001-10 μg/mL for 24 hours...
June 7, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28587437/overexpression-and-correlation-of-hif-2%C3%AE-vegfa-and-epha2-in-residual-hepatocellular-carcinoma-following-high-intensity-focused-ultrasound-treatment-implications-for-tumor-recurrence-and-progression
#11
Lun Wu, You-Shun Zhang, Meng-Liang Ye, Feng Shen, Wei Liu, Hong-Sheng Hu, Sheng-Wei Li, Hong-Wei Wu, Qin-Hua Chen, Wen-Bo Zhou
Rapid growth of residual tumors can occur as a result of their recurrence and progression. The present study aimed to investigate the expression of hypoxia inducible factor-2 subunit α (HIF-2α), vascular endothelial growth factor A (VEGFA), erythropoietin-producing hepatocellular A2 (EphA2) and angiogenesis in residual hepatocellular carcinoma (HCC), following treatment with high-intensity focused ultrasound (HIFU) ablation, in order to investigate the association between protein expression and tumor recurrence and growth...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28585531/small-extracellular-vesicles-secreted-from-senescent-cells-promote-cancer-cell-proliferation-through-epha2
#12
Masaki Takasugi, Ryo Okada, Akiko Takahashi, David Virya Chen, Sugiko Watanabe, Eiji Hara
Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation. However, the altered secretome of senescent cells can promote the growth of the surrounding cancer cells. Although extracellular vesicles (EVs) have emerged as new players in intercellular communication, their role in the function of senescent cell secretome has been largely unexplored. Here, we show that exosome-like small EVs (sEVs) are important mediators of the pro-tumorigenic function of senescent cells. sEV-associated EphA2 secreted from senescent cells binds to ephrin-A1, that is, highly expressed in several types of cancer cells and promotes cell proliferation through EphA2/ephrin-A1 reverse signalling...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28581527/targeting-epha2-impairs-cell-cycle-progression-and-growth-of-basal-like-triple-negative-breast-cancers
#13
W Song, Y Hwang, V M Youngblood, R S Cook, J M Balko, J Chen, D M Brantley-Sieders
Basal-like/triple-negative breast cancers (TNBCs) are among the most aggressive forms of breast cancer, and disproportionally affects young premenopausal women and women of African descent. Patients with TNBC suffer a poor prognosis due in part to a lack of molecularly targeted therapies, which represents a critical barrier for effective treatment. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for TNBC. EphA2 expression is enriched in the basal-like molecular subtype in human breast cancers...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28560458/epha2-receptor-activation-with-ephrin-a1-ligand-restores-cetuximab-efficacy-in-nras-mutant-colorectal-cancer-cells
#14
Elisabet Cuyàs, Bernardo Queralt, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Javier A Menendez
Patients with wild-type KRAS metastatic colorectal cancer (mCRC) that harbors NRAS activating mutations do not benefit from anti-EGFR therapies. Very little is known about oncogenic NRAS signaling driving mCRC unresponsiveness to the EGFR-directed antibody cetuximab. Using a system of paired NRAS-mutant and wild-type isogenic mCRC cell lines to explore signaling pathways engaged by the common oncogenic NRAS Q61K variant upon challenge with cetuximab, we uncovered an unexpected mechanism of resistance to cetuximab involving dysregulation of the ephrin-A1/EphA2 signaling axis...
May 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28552735/n-cadherin-regulates-signaling-mechanisms-required-for-lens-fiber-cell-elongation-and-lens-morphogenesis
#15
Caitlin M Logan, Suren Rajakaruna, Caitlin Bowen, Glenn L Radice, Michael L Robinson, A Sue Menko
Tissue development and regeneration involve high-ordered morphogenetic processes that are governed by elements of the cytoskeleton in conjunction with cell adhesion molecules. Such processes are particularly important in the lens whose structure dictates its function. Studies of our lens-specific N-cadherin conditional knockout mouse (N-cadcKO) revealed an essential role for N-cadherin in the migration of the apical tips of differentiating lens fiber cells along the apical surfaces of the epithelium, a region termed the Epithelial Fiber Interface (EFI), that is necessary for normal fiber cell elongation and the morphogenesis...
August 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28546337/pet-guided-evaluation-and-optimization-of-internalized-antibody-drug-conjugates-targeting-erythropoietin-producing-hepatoma-a2-receptor
#16
Orit Jacobson, Haojun Chen, Gang Niu, Dale O Kiesewetter, Qing Li, Gengcheng Yang, Kimberly Cook, Lan Xu, William Dall'Acqua, Ping Tsui, Li Peng, Xiaoyuan Chen
The erythropoietin producing hepatoma A2 receptor (EphA2) is a tyrosine kinase overexpressed by tumor stroma and cancer cells. High expression level of EphA2 predicts poor prognosis, correlating with disease progression and metastasis. Therefore, EphA2 is a relevant therapeutic target for human cancer. Antibodies, selectively bound to EphA2 receptor, can induce rapid receptor phosphorylation that results in antibody internalization and degradation. This internalization mechanism has been exploited with the development of antibody-drug conjugates (ADC) for cancer chemotherapy...
May 25, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28544567/chemoproteomics-aided-medicinal-chemistry-for-the-discovery-of-epha2-inhibitors
#17
Stephanie Heinzlmeir, Jonas Lohse, Tobias Treiber, Denis Kudlinzki, Verena Linhard, Santosh Lakshmi Gande, Sridhar Sreeramulu, Krishna Saxena, Xiaofeng Liu, Mathias Wilhelm, Harald Schwalbe, Bernhard Kuster, Guillaume Médard
The receptor tyrosine kinase EPHA2 has gained attention as a therapeutic drug target for cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small-molecule inhibitors. Herein we report the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor dasatinib as a lead structure. We designed hybrid structures of dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955, and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2...
June 21, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28523741/comparative-membrane-proteomics-analyses-of-breast-cancer-cell-lines-to-understand-the-molecular-mechanism-of-breast-cancer-brain-metastasis
#18
Wenjing Peng, Yu Zhang, Rui Zhu, Yehia Mechref
Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from 5 different breast cancer and a brain cancer cell lines...
May 19, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28507673/aiegen-based-theranostic-system-targeted-imaging-of-cancer-cells-and-adjuvant-amplification-of-antitumor-efficacy-of-paclitaxel
#19
Chao Chen, Zhegang Song, Xiaoyan Zheng, Zikai He, Bin Liu, Xuhui Huang, Deling Kong, Dan Ding, Ben Zhong Tang
Photosensitizers are generally treated as key components for photodynamic therapy. In contrast, we herein report an aggregation-induced emission luminogen (AIEgen)-based photosensitizer (TPE-Py-FFGYSA) that can serve as a non-toxic adjuvant to amplify the antitumor efficacy of paclitaxel, a well-known anticancer drug, with a synergistic effect of "0 + 1 > 1". Besides the adjuvant function, TPE-Py-FFGYSA can selectively light up EphA2 protein clusters overexpressed in cancer cells in a fluorescence turn-on mode, by taking advantage of the specific YSA peptide (YSAYPDSVPMMS)-EphA2 protein interaction...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28507312/design-and-evaluation-of-ephrina1-mutants-with-cerebral-protective-effect
#20
Yuanjun Zhu, Yuanqing Gao, Danping Zheng, Mengyang Shui, Kuai Yu, Xiaoyan Liu, Yuan Lin, Li Su, Wenxing Yang, Yinye Wang
The activation of EphA2 receptor by its natural ligand EphrinA1 causes blood brain barrier dysfunction, and inactivation of EphA2 reduces BBB damage in ischemic stroke. Thus, EphA2 targeted antagonists may serve as neuroprotective agents. We engineered four mutants of EphrinA1, EM1, EM2, EM3 and EM4, respectively. The computational analysis showed that these four mutants were capable of interacting with EphA2. Their potential neuroprotective effects were examined in mouse focal ischemia/reperfusion (I/R) model...
May 15, 2017: Scientific Reports
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