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https://www.readbyqxmd.com/read/29328373/integrative-gene-ontology-and-network-analysis-of-coronary-artery-disease-associated-genes-suggests-potential-role-of-erbb-pathway-gene-egfr
#1
Madankumar Ghatge, Jiny Nair, Ankit Sharma, Rajani Kanth Vangala
Coronary artery disease (CAD) is a major cause of mortality in India, more importantly the young Indians. Combinatorial and integrative approaches to evaluate pathways and genes to gain an improved understanding and potential biomarkers for risk assessment are required. Therefore, 608 genes from the CADgene database version 2.0, classified into 12 functional classes representing the atherosclerotic disease process, were analyzed. Homology analysis of the unique list of gene ontologies (GO) from each functional class gave 8 GO terms represented in 11 and 10 functional classes...
January 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328372/differential-microrna-expression-profiles-and-bioinformatics-analysis-between-young-and-aging-spontaneously-hypertensive-rats
#2
Jingfeng Wang, Jingjing Zhang, Xuefeng Ding, Yanyan Wang, Zhiming Li, Weipeng Zhao, Jianguo Jia, Jingmin Zhou, Junbo Ge
MicroRNAs (miRNAs/miRs) serve a role as important regulators in cardiac hypertrophy. The present study aimed to reveal the differential expression profile of miRNAs between young and aging spontaneously hypertensive rats (SHRs) and studied the functional annotation of predicted targets. Briefly, 3‑month‑old and 12‑month‑old SHRs (n=3/group) were subjected to echocardiography, histopathological analysis and dihydroethidium staining. Subsequently, small RNA sequencing and data processing was conducted to identify the differentially expressed miRNAs between these two groups...
January 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29321816/erbb-signaling-in-ctcs-of-ovarian-cancer-and-glioblastoma
#3
REVIEW
Anjali Geethadevi, Deepak Parashar, Erin Bishop, Sunila Pradeep, Pradeep Chaluvally-Raghavan
Circulating Tumor Cells (CTCs) are floating cell populations, which are resistant to anoikis after detachment from the primary sites and travel through the circulatory and lymphatic systems to disseminate throughout the body. CTCs are considered as seed cells for metastasis, and thus isolation of CTCs does not require any invasive procedure. Based on the nature and location of ovarian cancer and glioblastoma, the role of CTCs and hematogenous (carried by blood) spreading of tumor cells in these cancers were not understood well...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29321661/differential-recruitment-of-cd44-isoforms-by-erbb-ligands-reveals-an-involvement-of-cd44-in-breast-cancer
#4
Iris Morath, Christian Jung, Romain Lévêque, Chen Linfeng, Robert-Alain Toillon, Arne Warth, Véronique Orian-Rousseau
Members of the CD44 family of transmembrane glycoproteins control cell signaling pathways from numerous cell surface receptors, including receptor tyrosine kinases (RTKs). The decisive factor (ligand, RTKs or both) that controls the recruitment of specific CD44 isoforms is still unknown. We investigated this question by using the EGFR signaling pathway, in which one receptor can be activated by a broad range of ligands. By means of siRNA-mediated downregulation of CD44 expression and blocking experiments, we identified CD44v6 as a co-receptor for EGF- and ER-induced ErbB1 activation and for NRG1-induced ErbB3 and ErbB4 activation...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29319907/aberrant-accumulation-of-erbb4-in-progressive-supranuclear-palsy
#5
Aya Murakami, Masataka Nakamura, Satoshi Kaneko, Wen-Lang Lin, Dennis W Dickson, Hirofumi Kusaka
The human epidermal growth factor receptor family consists of 4 members that belong to the ErbB lineage of proteins (ErbB1-4). Neuregulin-1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP) METHODS: The brains of 10 PSP and 6 control patients were investigated by immunohistochemical analysis RESULTS: Whereas C-terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients...
January 10, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29312533/loss-of-pacs-2-delays-regeneration-in-dss-induced-colitis-but-does-not-affect-the-apcmin-model-of-colorectal-cancer
#6
Sarah L Dombernowsky, Jeanette Schwarz, Jacob Samsøe-Petersen, Reidar Albrechtsen, Kim B Jensen, Gary Thomas, Marie Kveiborg
PACS-2 is a multifunctional sorting protein that mediates cell homeostasis. We recently identified PACS-2 in a functional genome-wide siRNA screen for novel regulators of the metalloproteinase ADAM17, the main sheddase for ligands of the ErbB receptor family. Of note, we showed that Pacs2-/- mice have significantly reduced EGFR activity and proliferative index in the intestinal epithelium. As EGFR signaling is highly mitogenic for intestinal epithelial stem cells, and plays essential roles in intestinal epithelial regeneration and tumor development, we have now examined the role of PACS-2 in these processes...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305574/anti-trop2-blockade-enhances-the-therapeutic-efficacy-of-erbb3-inhibition-in-head-and-neck-squamous-cell-carcinoma
#7
Nathan Redlich, Anthony M Robinson, Kwangok P Nickel, Andrew P Stein, Deric L Wheeler, Douglas R Adkins, Ravindra Uppaluri, Randall J Kimple, Brian A Van Tine, Loren S Michel
ErbB3 has been widely implicated in treatment resistance, but its role as a primary treatment target is less clear. Canonically ErbB3 requires EGFR or ErbB2 for activation, whereas these two established treatment targets are thought to signal independently of ErbB3. In this study, we show that ErbB3 is essential for tumor growth of treatment-naive HNSCC patient-derived xenografts. This ErbB3 dependency occurs via ErbB3-mediated control of EGFR activation and HIF1α stabilization, which require ErbB3 and its ligand neuregulin-1...
January 5, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29301589/linking-foxo3-ncoa3-and-tcf7l2-to-ras-pathway-phenotypes-through-a-genome-wide-forward-genetic-screen-in-human-colorectal-cancer-cells
#8
Snehangshu Kundu, Muhammad Akhtar Ali, Niklas Handin, Narendra Padhan, Jimmy Larsson, Maria Karoutsou, Kenneth Ban, Jacek R Wiśniewski, Per Artursson, Liqun He, Mats Hellström, Tobias Sjöblom
BACKGROUND: The Ras pathway genes KRAS, BRAF, or ERBBs have somatic mutations in ~ 60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack mutations activating the Ras pathway or whether they have acquired mutations in genes hitherto unknown to belong to the pathway. METHODS: To address the second possibility and extend the compendium of Ras pathway genes, we used genome-wide transposon mutagenesis of two human colorectal cancer cell systems deprived of their activating KRAS or BRAF allele to identify genes enabling growth in low glucose, a Ras pathway phenotype, when targeted...
January 4, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29296175/organotypic-three-dimensional-cancer-cell-cultures-mirror-drug-responses-in-vivo-lessons-learned-from-the-inhibition-of-egfr-signaling
#9
Nico Jacobi, Rita Seeboeck, Elisabeth Hofmann, Helmut Schweiger, Veronika Smolinska, Thomas Mohr, Alexandra Boyer, Wolfgang Sommergruber, Peter Lechner, Corina Pichler-Huebschmann, Kamil Önder, Harald Hundsberger, Christoph Wiesner, Andreas Eger
Complex three-dimensional (3D) in vitro models that recapitulate human tumor biology are essential to understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellular communication, nutrient and oxygen gradients, and cell polarity that is lacking in two-dimensional (2D) monolayer cultures. In the present study, we demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29291395/erbb2-promotes-endothelial-phenotype-of-human-left-ventricular-epicardial-highly-proliferative-cells-ehipc
#10
Sergey Ryzhov, Michael P Robich, Daniel J Roberts, Amanda J Favreau-Lessard, Sarah M Peterson, Edward Jachimowicz, Rutwik Rath, Calvin P H Vary, Reed Quinn, Robert S Kramer, Douglas B Sawyer
The adult human heart contains a subpopulation of highly proliferative cells. The role of ErbB receptors in these cells has not been studied. From human left ventricular (LV) epicardial biopsies, we isolated highly proliferative cells (eHiPC) to characterize the cell surface expression and function of ErbB receptors in the regulation of cell proliferation and phenotype. We found that human LV eHiPC express all four ErbB receptor subtypes. However, the expression of ErbB receptors varied widely among eHiPC isolated from different subjects...
December 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29281081/hisp-a-hybrid-intelligent-approach-for-identifying-directed-signaling-pathways
#11
Xing-Ming Zhao, Shan Li
Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the signaling molecules of some signaling pathways have been determined. In this paper, we propose a novel hybrid intelligent method, namely HISP (Hybrid Intelligent approach for identifying directed Signaling Pathways), to determine both the topologies of signaling pathways and the direction of signaling flows within a pathway based on integer linear programming and genetic algorithm...
December 21, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29238610/a-role-for-erbb-signaling-in-the-induction-of-reactive-astrogliosis
#12
Jing Chen, Wanwan He, Xu Hu, Yuwen Shen, Junyan Cao, Zhengdong Wei, Yifei Luan, Li He, Fangdun Jiang, Yanmei Tao
Reactive astrogliosis is a hallmark of many neurological disorders, yet its functions and molecular mechanisms remain elusive. Particularly, the upstream signaling that regulates pathological responses of astrocytes is largely undetermined. We used a mouse traumatic brain injury model to induce astrogliosis and revealed activation of ErbB receptors in reactive astrocytes. Moreover, cell-autonomous inhibition of ErbB receptor activity in reactive astrocytes by a genetic approach suppressed hypertrophic remodeling possibly through the regulation of actin dynamics...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29233889/transcriptionally-inducible-pleckstrin-homology-like-domain-family-a-member-1-attenuates-erbb-receptor-activity-by-inhibiting-receptor-oligomerization
#13
Shigeyuki Magi, Kazunari Iwamoto, Noriko Yumoto, Michio Hiroshima, Takeshi Nagashima, Rieko Ohki, Amaya Garcia-Munoz, Natalia Volinsky, Alexander von Kriegsheim, Yasushi Sako, Koichi Takahashi, Shuhei Kimura, Boris N Kholodenko, Mariko Okada-Hatakeyama
Feedback control is a key mechanism in signal transduction, intimately involved in regulating the outcome of the cellular response. Here we report a novel mechanism by which PHLDA1, Pleckstrin homology-like domain, family A, member 1, negatively regulates ErbB receptor signaling by inhibition of receptor oligomerization. We have found that the ErbB3 ligand, heregulin, induces PHILDA1 expression in MCF-7 cells. Transcriptionally-induced PHLDA1 protein directly binds to ErbB3, while knockdown of PHLDA1 increases complex formation between ErbB3 and ErbB2...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29225480/role-of-afatinib-in-the-treatment-of-advanced-lung-squamous-cell-carcinoma
#14
REVIEW
Tiziana Vavalà
Lung cancer treatment has considerably changed over the last few years: the identification of druggable oncogenic alterations and innovative immunotherapic approaches granted lung cancer patients the possibility of more efficient and less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell carcinomas (SqCCs) patients have the chance to benefit from novel treatment alternatives, including immune checkpoint blockade and anti-angiogenic agents and, given positive trial results, from afatinib, a second generation tyrosine kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase receptors...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29218825/in-vivo-evidence-supporting-a-metastasis-suppressor-role-for-stard13-dlc2-in-erbb2-neu-oncogene-induced-mouse-mammary-tumours
#15
Pratima Basak, Heather Leslie, Rachelle L Dillon, William J Muller, Afshin Raouf, Michael Ra Mowat
Overexpression of dominant oncogenes and the loss of tumor suppressor genes are basic genetic events in the acquisition of the malignant phenotype. The erb-b2 receptor tyrosine kinase 2 (ERBB-2) proto-oncogene is overexpressed in 20-30% of human breast cancers. The StAR related lipid transfer domain containing 13 gene (STARD13), also known as Deleted in Liver Cancer-2 (DLC-2), maps to chromosome band 13q12.3 and is frequently downregulated in human cancers, including 72% of breast cancers. It encodes a RhoGAP protein with sterile α motif (SAM) and StAR-related lipid transfer (START) domains...
December 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29212203/knockdown-of-gtpbp4-inhibits-cell-growth-and-survival-in-human-hepatocellular-carcinoma-and-its-prognostic-significance
#16
Wen-Bin Liu, Wei-Dong Jia, Jin-Liang Ma, Ge-Liang Xu, Hang-Cheng Zhou, Yan Peng, Wei Wang
GTP-binding protein 4 (GTPBP4), as a novel member of GTPases involved in the synthesis of 60S subunit and maturation, is closely related to cell proliferation and growth. Till now, a small number of existing studies have found a contradictory dual role of GTPBP4 in cancer. Whether the expression level of GTPBP4 in hepatocellular carcinoma (HCC) is associated with the patients' prognosis or its function and underlying molecular mechanisms still remains unclear. In the present study, the above issues were explored for the first time...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207712/role-of-her-2-neu-in-premalignant-and-malignant-lesions-of-uterine-cervix
#17
Swasti Bajpai, Seema Awasthi, Shyamoli Dutta, Ankita Mittal, Ashutosh Kumar, Faiyaz Ahmad
Introduction: In light of literature and controversy that exists in various cervical lesions, this prospective study was designed to explore the expression of Human Epidermal Growth Factor Receptor-2 (HER-2/neu) in the cervical lesions and its correlation with the histopathological grade and type of tumour. Immunohistochemistry (IHC) was performed to evaluate HER-2/neu expression as it is the most reliable method of detecting overexpression of HER-2/neu. Aim: To assess the role of HER-2/neu expression in premalignant and malignant lesions of uterine cervix...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29199595/epidermal-growth-factor-receptor-tyrosine-kinase-a-potential-target-in-treatment-of-non-small-cell-lung-carcinoma
#18
REVIEW
Venugopal Vinod Prabhu, Niranjali Devaraj
Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung cancers are of the non-small-cell variety, which includes squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer progression is a requisite for determining which management approach-surgery, chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic approaches with antiangiogenic monoclonal antibodies or tyrosine kinase inhibitors are one option if tumors harbor oncogene mutations...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29190914/genomic-copy-number-gains-of-erbb-family-members-predict-poor-clinical-outcomes-in-glioma-patients
#19
Rui Liu, Yiping Qu, Lihong Chen, Jun Pu, Sharui Ma, Xiaozhi Zhang, Qi Yang, Bingyin Shi, Peng Hou, Meiju Ji
The aim of this study was to investigate copy number of ErbB family members (including EGFR, HER2, HER3 and HER4) in a cohort of gliomas and benign meningiomas (control subjects), and explore the associations of their copy number with clinicopathological characteristics and clinical outcomes of glioma patients. Using real-time quantitative PCR assay, we demonstrated that copy number of EGFR, HER2, HER3 and HER4 in glioma patients was significantly increased compared to control subjects. Moreover, our data also showed that the risk of cancer-related death was positively associated with copy number gain (CNG) of EGFR, HER3 and HER4, but not HER2...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190819/the-ectodomain-of-cadherin-11-binds-to-erbb2-and-stimulates-akt-phosphorylation-to-promote-cranial-neural-crest-cell-migration
#20
Ketan Mathavan, Vikram Khedgikar, Vanessa Bartolo, Dominique Alfandari
During development, a multi-potent group of cells known as the cranial neural crest (CNC) migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3) is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now...
2017: PloS One
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