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https://www.readbyqxmd.com/read/28455409/ddr1-receptor-tyrosine-kinase-promotes-prosurvival-pathway-through-notch1-activation
#1
Hyung-Gu Kim, So Young Hwang, Stuart A Aaronson, Anna Mandinova, Sam W Lee
No abstract text is available yet for this article.
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28391340/targeting-the-tyrosine-kinase-signalling-pathways-for-treatment-of-immune-mediated-glomerulonephritis-from-bench-to-bedside-and-beyond
#2
Terry King-Wing Ma, Stephen P McAdoo, Frederick Wai Keung Tam
Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28368050/tm4sf1-promotes-metastasis-of-pancreatic-cancer-via-regulating-the-expression-of-ddr1
#3
Jia-Chun Yang, Yi Zhang, Si-Jia He, Ming-Ming Li, Xiao-Lei Cai, Hui Wang, Lei-Ming Xu, Jia Cao
Transmembrane-4-L-six-family-1(TM4SF1), a four-transmembrane L6 family member, is highly expressed in various pancreatic cancer cell lines and promotes cancer cells metastasis. However, the TM4SF1-associated signaling network in metastasis remains unknown. In the present study, we found that TM4SF1 affected the formation and function of invadopodia. Silencing of TM4SF1 reduced the expression of DDR1 significantly in PANC-1 and AsPC-1 cells. Through double fluorescence immuno-staining and Co-immunoprecipitation, we also found that TM4SF1 colocalized with DDR1 and had an interaction with DDR1...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337325/tetrahydroisoquinoline-7-carboxamide-derivatives-as-new-selective-discoidin-domain-receptor-1-ddr1-inhibitors
#4
Zhen Wang, Yali Zhang, Sergio G Bartual, Jinfeng Luo, Tingting Xu, Wenting Du, Qiuju Xun, Zhengchao Tu, Rolf A Brekken, Xiaomei Ren, Alex N Bullock, Guang Liang, Xiaoyun Lu, Ke Ding
Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release in mouse primary peritoneal macrophages (MPMs)...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28259861/-investigation-of-cntf-comt-ddr1-disc1-drd2-drd3-and-dtnbp1-candidate-genes-in-schizophrenia-results-from-the-hungarian-schizobank-consortium
#5
Judit Benkovits, Szilvia Magyarosi, Attila J Pulay, Zoltan Makkos, Aniko Egerhazi, Nora Balogh, Peter Almos, Istvan Liko, Hungarian Schizobank Consortium, Gyorgy Nemeth, Judit Maria Molnar, Laszlo Nagy, Janos M Rethelyi
Schizophrenia is a chronic, debilitating psychiatric disorder characterized by heterogeneous clinical symptoms. Although the pathogenesis of this disorder is poorly understood, several lines of evidence support the role of both common and rare genetic variants in the etiology of schizophrenia. Common variants, single nucleotide polymorphisms can be investigated by candidate gene association studies or genome-wide association studies, while rare variants, single nucleotide variants are assessable by means of candidate gene resequencing or whole-exome and genome sequencing using next generation sequencing...
December 2016: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/28199848/discoidin-domain-receptor-1-mediates-myosin-dependent-collagen-contraction
#6
Nuno M Coelho, Pamma D Arora, Sander van Putten, Stellar Boo, Petar Petrovic, Alyna Xue Lin, Boris Hinz, Christopher A McCulloch
Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced >30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28198034/human-th17-migration-in-three-dimensional-collagen-involves-p38-mapk
#7
Maleck Kadiri, Mohammed-Amine El Azreq, Sofiane Berrazouane, Marc Boisvert, Fawzi Aoudjit
T cell migration across extracellular matrix (ECM) is an important step of the adaptive immune response but is also involved in the development of inflammatory autoimmune diseases. Currently, the molecular mechanisms regulating the motility of effector T cells in ECM are not fully understood. Activation of p38 MAPK has been implicated in T cell activation and is critical to the development of immune and inflammatory responses. In this study, we examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen...
February 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28143619/discoidin-domain-receptor-1-activity-drives-an-aggressive-phenotype-in-gastric-carcinoma
#8
Hoon Hur, In-Hye Ham, Dakeun Lee, Hyejin Jin, Kristina Y Aguilera, Hye Jeong Oh, Sang-Uk Han, Ji Eun Kwon, Young-Bae Kim, Ke Ding, Rolf A Brekken
BACKGROUND: Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that utilizes collagen as a ligand, is a key molecule in the progression of solid tumors as it regulates the interaction of cancer cells with the tumor stroma. However, the clinical relevance of DDR1 expression in gastric carcinoma is yet to be investigated. Here, we assessed the role of DDR1 in mediating the aggressive phenotype of gastric carcinoma and its potential as a therapeutic target. METHODS: We conducted DDR1 immunohistochemistry using a tissue microarray of 202 gastric carcinoma specimens...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28060374/heterogeneous-expression-of-the-collagen-receptor-ddr1-in-chronic-lymphocytic-leukaemia-and-correlation-with-progression
#9
G Barisione, M Fabbi, G Cutrona, L De Cecco, S Zupo, B Leitinger, M Gentile, M Manzoni, A Neri, F Morabito, M Ferrarini, S Ferrini
No abstract text is available yet for this article.
January 6, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/27915093/discoidin-domain-receptor-1-kinase-activity-is-required-for-regulating-collagen-iv-synthesis
#10
Corina M Borza, Yan Su, Truc-Linh Tran, Ling Yu, Nick Steyns, Kayla J Temple, Marcin J Skwark, Jens Meiler, Craig W Lindsley, Brennan R Hicks, Birgit Leitinger, Roy Zent, Ambra Pozzi
Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds to and is activated by collagens. DDR1 expression increases following kidney injury and accumulating evidence suggests that it contributes to the progression of injury. To this end, deletion of DDR1 is beneficial in ameliorating kidney injury induced by angiotensin infusion, unilateral ureteral obstruction, or nephrotoxic nephritis. Most of the beneficial effects observed in the DDR1-null mice are attributed to reduced inflammatory cell infiltration to the site of injury, suggesting that DDR1 plays a pro-inflammatory effect...
January 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27900042/antitumor-activity-of-7rh-a-discoidin-domain-receptor-1-inhibitor-alone-or-in-combination-with-dasatinib-exhibits-antitumor-effects-in-nasopharyngeal-carcinoma-cells
#11
Qiu-Ping Lu, Wen-Dan Chen, Jie-Ren Peng, Yao-Dong Xu, Qian Cai, Gong-Kan Feng, Ke Ding, Xiao-Feng Zhu, Zhong Guan
Dysregulation of the discoidin domain receptors (DDRs) has been implicated in the development of numerous types of tumors, including head and neck cancer, and nasopharyngeal, breast, ovarian and esophageal carcinomas. Furthermore, agents that inhibit DDR1 activity are hypothesized to be useful for the treatment of nasopharyngeal carcinoma (NPC). The aim of the present study was to evaluate the effect of the DDR1 inhibitory (3-(2-(pyrazolo(1,5-a)pyrimidin-6-yl)-ethynyl)benzamide compound, 7RH, in NPC cells both in vitro and in vivo, and its effect when used in combination with dasatinib, a SRC family kinase (SFK) inhibitor...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27843638/kras-driven-lung-adenocarcinoma-combined-ddr1-notch-inhibition-as-an-effective-therapy
#12
REVIEW
Chiara Ambrogio, Ernest Nadal, Alberto Villanueva, Gonzalo Gómez-López, Timothy P Cash, Mariano Barbacid, David Santamaría
Understanding the early evolution of cancer heterogeneity during the initial steps of tumorigenesis can uncover vulnerabilities of cancer cells that may be masked at later stages. We describe a comprehensive approach employing gene expression analysis in early lesions to identify novel therapeutic targets and the use of mouse models to test synthetic lethal drug combinations to treat human Kirsten rat sarcoma viral oncogene homologue (KRAS)-driven lung adenocarcinoma.
2016: ESMO Open
https://www.readbyqxmd.com/read/27824116/ddr1-promotes-e-cadherin-stability-via-inhibition-of-integrin-%C3%AE-1-src-activation-mediated-e-cadherin-endocytosis
#13
Hong-Ru Chen, Yi-Chun Yeh, Ching-Yi Liu, Yu-Ting Wu, Fang-Yu Lo, Ming-Jer Tang, Yang-Kao Wang
Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase of collagen, is primarily expressed in epithelial cells. Activation of DDR1 stabilises E-cadherin located on the cell membrane; however, the detailed mechanism of DDR1-stabilised E-cadherin remains unclear. We performed DDR1 knockdown (Sh-DDR1) on Mardin-Darby canine kidney cells to investigate the mechanism of DDR1-stabilised E-cadherin. Sh-DDR1 decreased junctional localisation, increased endocytosis of E-cadherin, and increased physical interactions between E-cadherin and clathrin...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822318/discovery-and-replication-of-a-peripheral-tissue-dna-methylation-biosignature-to-augment-a-suicide-prediction-model
#14
Makena L Clive, Marco P Boks, Christiaan H Vinkers, Lauren M Osborne, Jennifer L Payne, Kerry J Ressler, Alicia K Smith, Holly C Wilcox, Zachary Kaminsky
BACKGROUND: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27819674/mmtv-cre-ccn6-knockout-mice-develop-tumors-recapitulating-human-metaplastic-breast-carcinomas
#15
E E Martin, W Huang, T Anwar, C Arellano-Garcia, B Burman, J-L Guan, M E Gonzalez, C G Kleer
Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly downregulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse...
April 20, 2017: Oncogene
https://www.readbyqxmd.com/read/27723760/the-genomic-landscape-of-schwannoma
#16
Sameer Agnihotri, Shahrzad Jalali, Mark R Wilson, Arnavaz Danesh, Mira Li, George Klironomos, Jonathan R Krieger, Alireza Mansouri, Osaama Khan, Yasin Mamatjan, Natalie Landon-Brace, Takyee Tung, Mark Dowar, Tiantian Li, Jeffrey P Bruce, Kelly E Burrell, Peter D Tonge, Amir Alamsahebpour, Boris Krischek, Pankaj Kumar Agarwalla, Wenya Linda Bi, Ian F Dunn, Rameen Beroukhim, Michael G Fehlings, Vera Bril, Stefano M Pagnotta, Antonio Iavarone, Trevor J Pugh, Kenneth D Aldape, Gelareh Zadeh
Schwannomas are common peripheral nerve sheath tumors that can cause debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA sequencing of 125 samples uncovered, in addition to expected NF2 disruption, recurrent mutations in ARID1A, ARID1B and DDR1. RNA sequencing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis demonstrated the mechanism as resulting from a balanced 19-Mb chromosomal inversion on chromosome 10q...
November 2016: Nature Genetics
https://www.readbyqxmd.com/read/27720259/tgf-%C3%AE-1-promotes-linear-invadosome-formation-in-hepatocellular-carcinoma-cells-through-ddr1-up-regulation-and-collagen-i-cross-linking
#17
Zakaria Ezzoukhry, Elodie Henriet, Léo Piquet, Kevin Boyé, Paulette Bioulac-Sage, Charles Balabaud, Gabrielle Couchy, Jessica Zucman-Rossi, Violaine Moreau, Frédéric Saltel
Transforming growth factor-β1 (TGF-β1) is an important player in chronic liver diseases inducing fibrogenesis and hepatocellular carcinoma (HCC) development. TGF-β1 promotes pleiotropic modifications at the cellular and matrix microenvironment levels. TGF-β1 was described to enhance production of type I collagen and its associated cross-linking enzyme, the lysyl oxidase-like2 (LOXL2). In addition, TGF-β1 and type I collagen are potent inducers of invadosomes. Indeed, type I collagen fibers induce the formation of active linear invadosomes through the discoidin domain receptor 1 (DDR1)...
November 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/27718532/identification-of-mirsnps-associated-with-the-risk-of-multiple-myeloma
#18
Angelica Macauda, Diego Calvetti, Giuseppe Maccari, Kari Hemminki, Asta Försti, Hartmut Goldschmidt, Niels Weinhold, Richard Houlston, Vibeke Andersen, Ulla Vogel, Gabriele Buda, Judit Varkonyi, Anna Sureda, Joaquin Martinez Lopez, Marzena Watek, Aleksandra Butrym, Maria Eugenia Sarasquete, Marek Dudziński, Artur Jurczyszyn, Agnieszka Druzd-Sitek, Marcin Kruszewski, Edyta Subocz, Mario Petrini, Elzbieta Iskierka-Jażdżewska, Malgorzata Raźny, Gergely Szombath, Herlander Marques, Daria Zawirska, Dominik Chraniuk, Janusz Halka, Svend Erik Hove Jacobsen, Grzegorz Mazur, Ramón García Sanz, Charles Dumontet, Victor Moreno, Anna Stępień, Katia Beider, Matteo Pelosini, Rui Manuel Reis, Malgorzata Krawczyk-Kulis, Marcin Rymko, Hervé Avet-Loiseau, Fabienne Lesueur, Norbert Grząśko, Olga Ostrovsky, Krzysztof Jamroziak, Annette J Vangsted, Andrés Jerez, Waldemar Tomczak, Jan Maciej Zaucha, Katalin Kadar, Juan Sainz, Arnon Nagler, Stefano Landi, Federica Gemignani, Federico Canzian
Multiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression...
February 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27642041/compounds-from-polyphaga-plancyi-and-their-inhibitory-activities-against-jak3-and-ddr1-kinases
#19
Hong-Jie Zhu, Yong-Ming Yan, Zheng-Chao Tu, Jin-Feng Luo, Rui Liang, Tong-Hua Yang, Yong-Xian Cheng, Shu-Mei Wang
Plancyamides A (1) and B (3), plancypyrazine A (2), and plancyols A (4) and B (5), five new compounds (1-5), and three known ones (6-8), were isolated from the whole bodies of Polyphaga plancyi Bolivar. Their structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR, and HRESIMS. Among them, compound 3 is racemic, chiral HPLC separation afforded its respective enantiomers. The absolute configuration of 1 was assigned by computational methods. Biological evaluation of all the compounds with exception of 7 and 8 discloses that compounds 2 and 4 could inhibit JAK3 kinase with IC50 values of 12...
October 2016: Fitoterapia
https://www.readbyqxmd.com/read/27609387/-expression-and-significance-of-discoidin-domain-receptor-1-in-salivary-gland-mucoepidermoid-carcinoma
#20
Zhi-Ming Wang, Hui-Yuan Wen, Dong-Sheng Yang, Ming Ye, Ying Ma, Li-Ping Zhang
PURPOSE: To investigate the expression and significance of discoidin domain receptor 1 (DDR1) in salivary gland mucoepidermoid carcinoma (MEC). METHODS: Immunohistochemical and Western blot method were used to detect the expression of DDR1 in MEC M3SP2 and MC3 cell lines. Immunohistochemical method was used to detect the expression of DDR1 in 58 MEC and 20 normal salivary gland tissues. SPSS 13.0 software package was used for statistical analysis. RESULTS: The positive expression rate of DDR1 in salivary gland MEC tissues was 79...
June 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
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