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EPHA2

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https://www.readbyqxmd.com/read/28631589/comparison-of-protein-expression-during-wild-type-and-e1b-55k-deletion-adenovirus-infection-using-quantitative-time-course-proteomics
#1
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 20, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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...
May 26, 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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28505517/a-modified-adenovirus-vector-mediated-antibody-screening-method-identifies-epha2-as-a-cancer-target
#15
Toshihiro Tanaka, Hiromi Yamada, Masahide Kuroki, Shohta Kodama, Kazuo Tamura, Yasushi Takamatsu
BACKGROUND: We constructed a genetically modified adenovirus vector incorporating an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33). Adv-FZ33 allows an antibody to redirect the vector to a target molecule on the cell surface. We attempted to search for target antigen candidates and antibodies that allowed highly selective gene transduction into malignant tumors. METHODS: Hybridoma libraries producing monoclonal antibodies (mAbs) were screened that increased transduction efficiency in cancer cell lines after cross-linking with Adv-FZ33...
May 12, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28487392/epha2-expression-regulates-inflammation-and-fibroproliferative-remodeling-in-atherosclerosis
#16
Alexandra C Finney, Steven D Funk, Jonette Green, Arif Yurdagul, Mohammad A Rana, Rebecca Pistorius, Miriam Henry, Andrew D Yurochko, Christopher B Pattillo, James G Traylor, Jin Chen, Matthew D Woolard, Christopher G Kevil, A Wayne Orr
Background -Atherosclerotic plaque formation results from chronic inflammation and fibroproliferative remodeling in the vascular wall. We previously demonstrated that both human and mouse atherosclerotic plaques show elevated expression of EphA2, a guidance molecule involved in cell-cell interactions and tumorigenesis. Methods -Here, we assessed EphA2's role in atherosclerosis by deleting EphA2 in a mouse model of atherosclerosis (Apoe(-/-)) and by assessing EphA2 function in multiple vascular cell culture models...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28472014/protection-by-the-eph-ephrin-system-against-mesenteric-ischemia-reperfusion-injury
#17
Valentina Vivo, Irene Zini, Anna Maria Cantoni, Andrea Grandi, Massimiliano Tognolini, Riccardo Castelli, Vigilio Ballabeni, Simona Bertoni, Elisabetta Barocelli
Mesenteric ischemia-reperfusion (I/R)-induced injury targets primarily endothelial and epithelial cells, leading to a cascade of inflammatory events, eventually culminating in life-threatening syndromes. Hitherto, the role of Eph, the largest family of tyrosine kinase receptors, and of their cell-bound ephrin ligands, whose interaction generates a bidirectional signaling, is still debated in I/R injury. The aim of the present work was therefore to investigate the effects produced by unidirectional activation of forward signaling (administration of chimeric protein ephrinA1-Fc), of reverse signaling (EphA2-Fc), or inhibition of both signals (monomeric EphA2 and the protein-protein interaction inhibitor UniPR1331) on the local and systemic inflammatory responses triggered by mesenteric I/R in mice...
May 2, 2017: Shock
https://www.readbyqxmd.com/read/28435450/exome-sequencing-of-oral-squamous-cell-carcinoma-reveals-molecular-subgroups-and-novel-therapeutic-opportunities
#18
Shih-Chi Su, Chiao-Wen Lin, Yu-Fan Liu, Wen-Lang Fan, Mu-Kuan Chen, Chun-Ping Yu, Wei-En Yang, Chun-Wen Su, Chun-Yi Chuang, Wen-Hsiung Li, Wen-Hung Chung, Shun-Fa Yang
Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features...
2017: Theranostics
https://www.readbyqxmd.com/read/28418495/molecular-genetic-analysis-of-pakistani-families-with-autosomal-recessive-congenital-cataracts-by-homozygosity-screening
#19
Jianjun Chen, Qiwei Wang, Patricia E Cabrera, Zilin Zhong, Wenmin Sun, Xiaodong Jiao, Yabin Chen, Gowthaman Govindarajan, Muhammad Asif Naeem, Shaheen N Khan, Muhammad Hassaan Ali, Muhammad Zaman Assir, Fawad Ur Rahman, Zaheeruddin A Qazi, Sheikh Riazuddin, Javed Akram, S Amer Riazuddin, J Fielding Hejtmancik
Purpose: To identify the genetic origins of autosomal recessive congenital cataracts (arCC) in the Pakistani population. Methods: Based on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28414140/shear-stress-inhibits-il-17a-mediated-induction-of-osteoclastogenesis-via-osteocyte-pathways
#20
Chongshan Liao, Tianfan Cheng, Shuai Wang, Chengfei Zhang, Lijian Jin, Yanqi Yang
Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells...
April 14, 2017: Bone
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