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https://www.readbyqxmd.com/read/28102297/whsc1l1-mediated-egfr-mono-methylation-enhances-the-cytoplasmic-and-nuclear-oncogenic-activity-of-egfr-in-head-and-neck-cancer
#1
Vassiliki Saloura, Theodore Vougiouklakis, Makda Zewde, Xiaolan Deng, Kazuma Kiyotani, Jae-Hyun Park, Yo Matsuo, Mark Lingen, Takehiro Suzuki, Naoshi Dohmae, Ryuji Hamamoto, Yusuke Nakamura
While multiple post-translational modifications have been reported to regulate the function of epidermal growth factor receptor (EGFR), the effect of protein methylation on its function has not been well characterized. In this study, we show that WHSC1L1 mono-methylates lysine 721 in the tyrosine kinase domain of EGFR, and that this methylation leads to enhanced activation of its downstream ERK cascade without EGF stimulation. We also show that EGFR K721 mono-methylation not only affects the function of cytoplasmic EGFR, but also that of nuclear EGFR...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101945/epidermal-growth-factor-receptor-egfr-mapk-nuclear-factor-nf-%C3%AE%C2%BAb-il8-a-possible-mechanism-of-particulate-matter-pm-2-5-induced-lung-toxicity
#2
Seung-Chan Jeong, Yoon Cho, Mi-Kyung Song, Eunil Lee, Jae-Chun Ryu
Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2...
January 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28101233/lipid-raft-localization-of-epidermal-growth-factor-receptor-alters-matrix-metalloproteinase-1-expression-in-siha-cells-via-the-mapk-erk-signaling-pathway
#3
Zongfeng Zhang, Lina Wang, Juan Du, Yuanbo Li, Huilun Yang, Chenxi Li, Hui Li, Haiyang Hu
Matrix metalloproteinase-1 (MMP-1) has been identified as an important participant in tumor invasion, metastasis and angiogenesis. The purpose of the present study was to investigate the effects of epidermal growth factor receptor (EGFR) localization to lipid rafts on signaling pathways involved in the regulation of MMP-1 expression in SiHa cells, a cervical cancer cell line. EGFR activation by EGF specifically induced MMP-1 expression at both the messenger RNA and protein levels. Additionally, it was observed that EGFR localized to lipid rafts, and that the redistribution of EGFR induced by lipid raft disruption strengthened EGF-induced MMP-1 expression...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100485/quantification-of-growth-factor-signaling-and-pathway-crosstalk-by-live-cell-imaging
#4
Sean M Gross, Peter Rotwein
Peptide growth factors stimulate cellular responses through activation of their trans-membrane receptors. Multiple intracellular signaling cascades are engaged following growth factor - receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation, but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluorescent live-cell imaging reporters that are readouts for two major growth factor-stimulated pathways, Ras - Raf - Mek - Erk and PI3-kinase - Akt...
January 18, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28099130/epidermal-growth-factor-receptor-egfr-involvement-in-successful-growth-hormone-gh-signaling-in-gh-transduction-defect
#5
Eirini Kostopoulou, Andrea Paola Rojas-Gil, Alexia Karvela, Bessie E Spiliotis
BACKGROUND: Growth hormone (GH) transduction defect (GHTD) is a growth disorder with impaired signal transducer and activator of transcription 3 (STAT3) phosphorylation mediated by overexpression of cytokine-inducible SH2-containing protein (CIS), which causes increased growth hormone receptor (GHR) degradation. This study investigated the role of epidermal growth factor (EGF) in the restoration of normal GH signaling in GHTD. METHODS: Protein expression, cellular localization and physical contact of proteins of the GH and EGF signaling pathways were studied by Western immunoblotting, immunofluorescence and co-immunoprecipitation, respectively...
January 18, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28098905/cripto-1-promotes-epithelial-mesenchymal-transition-in-prostate-cancer-via-wnt-%C3%AE-catenin-signaling
#6
Yan Liu, Zhenbang Qin, Kuo Yang, Ranlu Liu, Yong Xu
The Cripto-1 (CR-1) derived EGF-CFC family was overexpressed in tumor development enhancing proliferation, epithelial-mesenchymal transition (EMT) and migration of tumor cells. However, correlation between CR-1 and prostate cancer (PCa) remains still unclear. In the present study, we proved that CR-1 was expressed in PCa and its function was in the progression of PCa. Compared with benign prostatic hyperplasia (BPH) tissues, we confirmed that PCa tissues had high expression of CR-1 by immunohistochemistry and statistical data showed that CR-1 promoted properties of EMT in PCa tissues, including the downregulation of the cell adhesion molecules β-catenin (membrane) and E-cadherin while upregulating transcription factors β-catenin...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098871/lectin-pcl-inhibits-the-warburg-effect-of-pc3-cells-by-combining-with-egfr-and-inhibiting-hk2
#7
Hong Zhang, Xia Du, Ting-Ting Sun, Chun-Liu Wang, Ye Li, Shou-Zhen Wu
Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098310/a-computational-model-predicts-genetic-nodes-that-allow-switching-between-species-specific-responses-in-a-conserved-signaling-network
#8
Adriana T Dawes, David Wu, Karley K Mahalak, Edward M Zitnik, Natalia Kravtsova, Haiwei Su, Helen M Chamberlin
Cell signaling networks regulate a variety of developmental and physiological processes, and changes in their response to external stimuli are often implicated in disease initiation and progression. To elucidate how different responses can arise from conserved signaling networks, we have developed a mathematical model of the well-characterized Caenorhabditis vulval development network involving EGF, Wnt and Notch signaling that recapitulates biologically observed behaviors. We experimentally block a specific element of the EGF pathway (MEK), and find different behaviors in vulval development in two Caenorhabditis species, C...
January 18, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28095743/adult-murine-pancreatic-progenitors-require-egf-and-nicotinamide-for-self-renewal-and-differentiation-in-a-serum-and-conditioned-medium-free-culture
#9
Lena Wedeken, Angela Luo, Jacob R Tremblay, Jeffrey Rawson, Liang Jin, Dan Gao, Janine Quijano, Hsun Teresa Ku
Adult pancreatic stem and progenitor cells may serve as an alternative source of insulin-secreting endocrine cells in cell replacement therapy for type 1 diabetes, but much remained unknown about these cells. We previously identified adult murine pancreatic progenitor-like cells that displayed in vitro self-renewal and tri-lineage differentiation activities in a 3-dimensional colony/organoid assay containing 1% methylcellulose and 5% Matrigel. However, the presence of other undefined culture components, such as serum and conditioned medium, has prevented a complete understanding of the signals required for progenitor cell growth...
January 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28094771/orphan-gpr182-suppresses-erk-mediated-intestinal-proliferation-during-regeneration-and-adenoma-formation
#10
Daniel O Kechele, R Eric Blue, Bailey Zwarycz, Scott T Espenschied, Amanda T Mah, Marni B Siegel, Charles M Perou, Shengli Ding, Scott T Magness, P Kay Lund, Kathleen M Caron
Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28092674/a-targetable-hb-egf-cited4-axis-controls-oncogenesis-in-lung-cancer
#11
C-H Hsieh, Y-T Chou, M-H Kuo, H-P Tsai, J-L Chang, C-W Wu
Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092656/influence-of-node-abundance-on-signaling-network-state-and-dynamics-analyzed-by-mass-cytometry
#12
Xiao-Kang Lun, Vito R T Zanotelli, James D Wade, Denis Schapiro, Marco Tognetti, Nadine Dobberstein, Bernd Bodenmiller
Signaling networks are key regulators of cellular function. Although the concentrations of signaling proteins are perturbed in disease states, such as cancer, and are modulated by drug therapies, our understanding of how such changes shape the properties of signaling networks is limited. Here we couple mass-cytometry-based single-cell analysis with overexpression of tagged signaling proteins to study the dependence of signaling relationships and dynamics on protein node abundance. Focusing on the epidermal growth factor receptor (EGFR) signaling network in HEK293T cells, we analyze 20 signaling proteins during a 1-h EGF stimulation time course using a panel of 35 antibodies...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28092052/real-time-single-molecule-visualization-of-sh2-domain-membrane-recruitment-in-growth-factor-stimulated-cells
#13
Dongmyung Oh
In the last decade, single molecule tracking (SMT) techniques have emerged as a versatile tool for molecular cell biology research. This approach allows researchers to monitor the real-time behavior of individual molecules in living cells with nanometer and millisecond resolution. As a result, it is possible to visualize biological processes as they occur at a molecular level in real time. Here we describe a method for the real-time visualization of SH2 domain membrane recruitment from the cytoplasm to epidermal growth factor (EGF) induced phosphotyrosine sites on the EGF receptor...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28090808/biomaterial-encapsulation-is-enhanced-in-the-early-stages-of-the-foreign-body-reaction-during-conditional-macrophage-depletion-in-transgenic-mafia-mice
#14
Ruud A Bank, Jurjen Zandstra, Hilde Room, Arjen H Petersen, Sander Maarten van Putten
Macrophages are pivotal cells during the foreign body reaction, as they orchestrate the pro-inflammatory microenvironment inside and around biomaterials by secretion of inflammatory mediators. Furthermore they are responsible for the degradation of biomaterials and are thought to instruct the fibroblasts that generate a fibrous capsule around implanted biomaterials. In this study we investigated the events during the FBR when macrophages are not present. Hexamethylenediisocyanate cross-linked collagen scaffolds were implanted in "Macrophage Fas-Induced Apoptosis" (MaFIA) mice, which allow "on demand" macrophage depletion...
January 15, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28090686/effectively-enhancing-cytotoxic-and-apoptotic-effects-of-alpha-momorcharin-by-integrating-a-heparin-binding-peptide
#15
Meng-Jie Tan, Xue-Wei Cao, Peng-Fei Li, Yi-Zhou Zhai, Yu Zhou, Ye-Jun Liu, Jian Zhao, Fu-Jun Wang
Alpha-momorcharin (α-MMC), a type I ribosome inactivating protein, has attracted a great deal attention because of its antitumor activity. However, the cytotoxicity of α-MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of α-MMC, a heparin-binding domain derived from HB-EGF (named HBP) was used as a cell-penetrating peptide and fused to the C-terminus of α-MMC. This novel α-MMC-HBP fusion protein was expressed and purified with a Ni(2+) -resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of α-MMC...
January 16, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28089742/multiple-habp2-variants-in-familial-papillary-thyroid-carcinoma-contribution-of-a-group-of-thyroid-checked-controls
#16
Benjamin Kern, Lucie Coppin, Pauline Romanet, Michel Crépin, Isabelle Szuster, Florence Renaud, Emmanuelle Leteurtre, Frédéric Frénois, Jean-Louis Wemeau, Bruno Carnaille, Catherine Cardot-Bauters, Christine Do Cao, Pascal Pigny
A heterozygous germline variant in the HABP2 gene c.1601G > A (p.Gly534Glu), which negatively impacts its tumor suppressive activity in vitro, has been described in 4-14% of kindreds of European-American ancestry with familial papillary thyroid carcinoma (fPTC). But it is also found in ≈4% of Europeans and European/Americans from public databases that, however, did not provide information on the thyroid function of the controls. To get unbiased results, we decided to compare HABP2 genotypes of patients with fPTC with those of "thyroid-checked" controls...
January 9, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28089369/deciphering-the-fringe-mediated-notch-code-identification-of-activating-and-inhibiting-sites-allowing-discrimination-between-ligands
#17
Shinako Kakuda, Robert S Haltiwanger
Fringe proteins are β3-N-acetylglucosaminyltransferases that modulate Notch activity by modifying O-fucose residues on epidermal growth factor-like (EGF) repeats of Notch. Mammals have three Fringes: Lunatic, Manic, and Radical. While Lunatic and Manic Fringe inhibit Notch1 activation from Jagged1 and enhance activation from Delta-like 1, Radical Fringe enhances signaling from both. We used a mass spectrometry approach to determine whether the variable effects of Fringes on Notch1 result from generation of unique glycosylation patterns on Notch1...
December 29, 2016: Developmental Cell
https://www.readbyqxmd.com/read/28089234/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#18
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28089174/neonatal-acute-kidney-injury-severity-and-recovery-prediction-and-the-role-of-serum-and-urinary-biomarkers
#19
Deirdre U Sweetman
Neonatal acute kidney injury is common, in part due to incomplete renal maturation and also due to frequent exposure to risk factors for acute kidney injury such as perinatal asphyxia, extracorporeal-membrane-oxygenation, cardiac surgery, sepsis, prematurity and nephrotoxicity. However the current method by which acute kidney injury is diagnosed is sub-optimal and not universally accepted which impairs the accurate estimation of the true incidence of neonatal acute kidney injury. Serum Cystatin-C, urinary NGAL, KIM-1 and IL-18 are promising neonatal acute kidney injury biomarkers however the diagnosis of acute kidney injury remains serum creatinine/urine output-based in many studies...
January 11, 2017: Early Human Development
https://www.readbyqxmd.com/read/28088463/stress-induced-egf-receptor-signaling-through-stat3-and-tumor-progression-in-triple-negative-breast-cancer
#20
Nikolas Balanis, Cathleen R Carlin
Elevated STAT3 activity is a hallmark of many epithelial carcinomas particularly in breast cancers where it is known to contribute to tumor progression through a variety of context-dependent biological responses. However, its role downstream of stress-exposed EGF receptors (EGFR) that are transactivated in endosomes independent of exogenous ligand has not been studied. This review discusses how STAT3 signaling induced by therapeutic stress in EGFR-driven triple-negative breast cancers (TNBC) might override normal epithelial homeostatic mechanisms and provide a survival advantage for tumor cells before they leave the primary tumor and spread to distant sites...
January 11, 2017: Molecular and Cellular Endocrinology
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