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https://www.readbyqxmd.com/read/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#1
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28597949/primary-islet-autoantibody-at-initial-seroconversion-and-autoantibodies-at-diagnosis-of-type-1-diabetes-as-markers-of-disease-heterogeneity
#2
Jorma Ilonen, Johanna Lempainen, Anna Hammais, Antti-Pekka Laine, Taina Härkönen, Jorma Toppari, Riitta Veijola, Mikael Knip
OBJECTIVE: The relationship between patterns of islet autoantibodies at diagnosis and specificity of the first islet autoantibody at the initiation of autoimmunity was analyzed with the aim of identifying patterns informative of the primary autoantibodies. METHODS: Information about a single first autoantibody at seroconversion and autoantibody data at diagnosis were available for 128 children participating in the follow-up cohort of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study...
June 9, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28591206/erbb3-a-potential-serum-biomarker-for-early-detection-and-therapeutic-target-for-devil-facial-tumour-1-dft1
#3
Dane A Hayes, Dale A Kunde, Robyn L Taylor, Stephen B Pyecroft, Sukhwinder Singh Sohal, Elizabeth T Snow
Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1's cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored...
2017: PloS One
https://www.readbyqxmd.com/read/28590931/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#4
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590920/hcarg-commd5-inhibits-erbb-receptor-driven-renal-cell-carcinoma
#5
Hiroyuki Matsuda, Carole G Campion, Kyoko Fujiwara, Jin Ikeda, Suzanne Cossette, Thomas Verissimo, Maiko Ogasawara, Louis Gaboury, Kosuke Saito, Kenya Yamaguchi, Satoru Takahashi, Morito Endo, Noboru Fukuda, Masayoshi Soma, Pavel Hamet, Johanne Tremblay
Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28570571/construction-and-analyses-of-the-microrna-target-gene-differential-regulatory-network-in-thyroid-carcinoma
#6
Ying-Ying Kang, Yang Liu, Ming-Li Wang, Min Guo, Yan Wang, Zhi-Feng Cheng
Thyroid-carcinoma (THCA) is the most common malignancy with an increasing incidence. Recent evidence has emphasized the role of microRNA (miRNA) in THCA. However, knowledge concerning the roles of miRNAs in THCA is still limited. We therefore use a miRNA-target gene differential regulatory network (MGDRN) to identify key miRNAs and characterize their synergistic regulation in THCA. Both miRNA-target gene interactions from multiple databases and negative expression correlations between miRNA-target genes were used to characterize the interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28570276/macrophage-infiltration-and-genetic-landscape-of-undifferentiated-uterine-sarcomas
#7
Joanna Przybyl, Magdalena Kowalewska, Anna Quattrone, Barbara Dewaele, Vanessa Vanspauwen, Sushama Varma, Sujay Vennam, Aaron M Newman, Michal Swierniak, Elwira Bakuła-Zalewska, Janusz A Siedlecki, Mariusz Bidzinski, Jan Cools, Matt van de Rijn, Maria Debiec-Rychter
Endometrial stromal tumors include translocation-associated low- and high-grade endometrial stromal sarcomas (ESS) and highly malignant undifferentiated uterine sarcomas (UUS). UUS is considered a poorly defined group of aggressive tumors and is often seen as a diagnosis of exclusion after ESS and leiomyosarcoma (LMS) have been ruled out. We performed a comprehensive analysis of gene expression, copy number variation, point mutations, and immune cell infiltrates in the largest series to date of all major types of uterine sarcomas to shed light on the biology of UUS and to identify potential novel therapeutic targets...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28542518/rnf41-interacts-with-the-vps52-subunit-of-the-garp-and-earp-complexes
#8
Delphine Masschaele, Leentje De Ceuninck, Joris Wauman, Dieter Defever, Frank Stenner, Sam Lievens, Frank Peelman, Jan Tavernier
RNF41 (Ring Finger Protein 41) is an E3 ubiquitin ligase involved in the intracellular sorting and function of a diverse set of substrates. Next to BRUCE and Parkin, RNF41 can directly ubiquitinate ErbB3, IL-3, EPO and RARα receptors or downstream signaling molecules such as Myd88, TBK1 and USP8. In this way it can regulate receptor signaling and routing. To further elucidate the molecular mechanism behind the role of RNF41 in intracellular transport we performed an Array MAPPIT (Mammalian Protein-Protein Interaction Trap) screen using an extensive set of proteins derived from the human ORFeome collection...
2017: PloS One
https://www.readbyqxmd.com/read/28522256/sporadic-early-onset-diffuse-gastric-cancers-have-high-frequency-of-somatic-cdh1-alterations-but-low-frequency-of-somatic-rhoa-mutations-compared-with-late-onset-cancers
#9
Soo Young Cho, Jun Won Park, Yang Liu, Young Soo Park, Ju Hee Kim, Hanna Yang, Hyejin Um, Woo Ri Ko, Byung Il Lee, Sun Young Kwon, Seung Wan Ryu, Chae Hwa Kwon, Do Youn Park, Jae-Hyuk Lee, Sang Il Lee, Kyu Sang Song, Hoon Hur, Sang-Uk Han, Heekyung Chang, Su-Jin Kim, Byung-Sik Kim, Jeong-Hwan Yook, Moon-Won Yoo, Beom-Su Kim, In-Seob Lee, Myeong-Cherl Kook, Nina Thiessen, An He, Chip Stewart, Andrew Dunford, Jaegil Kim, Juliann Shih, Gordon Saksena, Andrew D Cherniack, Steven Schumacher, Amaro-Taylor Weiner, Mara Rosenberg, Gad Getz, Eun Gyeong Yang, Min Hee Ryu, Adam J Bass, Hark Kyun Kim
BACKGROUND & AIMS: Early-onset gastric cancer, which develops in younger patients than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea...
May 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28514724/sirna-mediated-inactivation-of-her3-improves-the-antitumour-activity-and-sensitivity-of-gefitinib-in-gastric-cancer-cells
#10
Heng-Heng Yuan, Ying-Nan Yang, Jian-Hua Zhou, Yan-Jing Li, Li-Ying Wang, Jun-Wei Qin, Tao Liu, Zhen-Zhen Li, Qing-Xin Zhou, Xiao-Li Wei, Ting-Ting Zhang, Peng Huang, Wen-Jie Zhang, Lei Liu, Xiao-Xue Du, Yu Han
The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing antibodies and alternative inhibitors of HER3 have been sought as cancer therapeutics. Here, we describe the stable suppression of HER3 mRNA and protein using siRNA...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480322/data-on-the-effect-of-in-vivo-knockdown-using-artificial-erbb3-mirna-on-remak-bundle-structure
#11
Yuki Miyamoto, Tomohiro Torii, Kazuko Kawahara, Masashi Inoue, Takako Morimoto, Masahiro Yamamoto, Junji Yamauchi
Mature Schwann cells, the peripheral nervous system (PNS) glial cells, have two major roles for neuronal axons (Bunge, 1993) [1]. For large diameter axons, Schwann cells form myelin sheaths with multiple layers. For small diameter axons, they form Remak bundle composed only of single layer of the Schwann cell plasma membrane. In the PNS, ErbB3 forms a dimer with ErbB2 on the Schwann cell plasma membrane. ErbB3 plays a key role in myelination by myelinating Schwann cells, that is to say, its role in myelin thickness...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28469731/integrated-data-analysis-reveals-potential-drivers-and-pathways-disrupted-by-dna-methylation-in-papillary-thyroid-carcinomas
#12
Caroline Moraes Beltrami, Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fabio Albuquerque Marchi, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto
BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC paired with non-neoplastic adjacent tissues (NT) was carried out to identify and contribute to the elucidation of the role of novel genic and intergenic regions beyond those described in the promoter and CpG islands (CGI)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28450158/the-erbb-family-and-androgen-receptor-signaling-are-targets-of%C3%A2-celecoxib-in-prostate-cancer
#13
Antonella Brizzolara, Roberto Benelli, Roberta Venè, Paola Barboro, Alessandro Poggi, Francesca Tosetti, Nicoletta Ferrari
Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#14
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters, and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28423512/kinase-analysis-of-penile-squamous-cell-carcinoma-on-multiple-platforms-to-identify-potential-therapeutic-targets
#15
Eddy S Yang, Christopher D Willey, Amitkumar Mehta, Michael R Crowley, David K Crossman, Dongquan Chen, Joshua C Anderson, Gurudatta Naik, Deborah L Della Manna, Tiffiny S Cooper, Guru Sonpavde
Penile squamous cell carcinoma (PSCC) is an orphan malignancy with poorly understood biology and suboptimal systemic therapy. Given that kinases may be drivers and readily actionable, we performed comprehensive multiplatform analysis of kinases in PSCC tumor and normal tissue. Fresh frozen tumors were collected from 11 patients with PSCC. After macrodissection to demarcate tumor from normal tissue, the samples underwent multiplatform analysis of kinases. Next Generation Sequencing (NGS) of 517 kinase genes was performed using Agilent Kinome capture and run on the Illumina MiSeq at PE150bp...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421882/inhibition-of-her3-activation-and-tumor-growth-with-a-human-antibody-binding-to-a-conserved-epitope-formed-by-domain-iii-and-iv
#16
Lisa C Schmitt, Alexander Rau, Oliver Seifert, Jonas Honer, Meike Hutt, Simone Schmid, Jonas Zantow, Michael Hust, Stefan Dübel, Monilola A Olayioye, Roland E Kontermann
Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged as relevant target for antibody-mediated tumor therapy. Here, we describe a novel human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and parts of domain IV of the extracellular region of HER3, conserved between HER3 and mouse ErbB3. An affinity of 11 nM was determined for the monovalent interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50 values in the low picomolar range (27 - 83 pM)...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#17
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynaecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
July 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28399526/expression-of-the-erbb-family-of-ligands-and-receptors-in-gastric-cancer
#18
Sun-Ju Byeon, Hye Seung Lee, Min-A Kim, Byung Lan Lee, Woo Ho Kim
OBJECTIVE: Gastric cancer (GC) is the second most common cancer and the third leading cause of cancer-related death in Korea. Alterations in the ERBB (homology to the erythroblastoma viral gene product, v-erbB) receptor family and ERBB-related signaling pathways are frequently observed in GC. However, the roles of the ERBB receptors and their ligands in GC are not well established. METHODS: We evaluated the expression levels of various ERBB receptor ligands (i.e...
April 12, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28388586/her2-and-egfr-amplification-and-expression-in-urothelial-carcinoma-occurs-in-distinct-biological-and-molecular-contexts
#19
Pontus Eriksson, Gottfrid Sjödahl, Gunilla Chebil, Fredrik Liedberg, Mattias Höglund
We analyzed a cohort of 599 cases of urothelial carcinoma for EGFR, ERBB2, and ERBB3 gene expression and genomic alterations. The cohort consisted of a reference set (n = 292) comprising all stages and grades and one set (n = 307) of advanced tumors. All cases were previously classified into urothelial carcinoma molecular subtypes. Genomic amplifications were established by array-CGH or in-situ hybridization, and gene expression both at mRNA and protein levels. Clinical HER2 status was independently evaluated using standard clinical procedures...
March 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28369073/her2-signaling-regulates-her2-localization-and-membrane-retention
#20
Jaekwang Jeong, Wonnam Kim, Lark Kyun Kim, Joshua VanHouten, John J Wysolmerski
ErbB2/HER2/Neu is a receptor tyrosine kinase that is overexpressed in 25-30% of human breast cancers, usually associated with amplification of the ERBB2 gene. HER2 has no recognized ligands and heterodimers between HER2 and EGFR (ErbB1/HER1) or HER2 and ErbB3/HER3 are important in breast cancer. Unlike other ErbB family members, HER2 is resistant to internalization and degradation, and remains at the cell surface to signal for prolonged periods after it is activated. Although the mechanisms underlying retention of HER2 at the cell surface are not fully understood, prior studies have shown that, in order to avoid internalization, HER2 must interact with the chaperone, HSP90, and the calcium pump, PMCA2, within specific plasma membrane domains that protrude from the cell surface...
2017: PloS One
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