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Discoidin domain receptor

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https://www.readbyqxmd.com/read/28396848/update-on-the-treatment-of-metastatic-squamous-non-small-cell-lung-cancer-in-new-era-of-personalized-medicine
#1
REVIEW
Sara Victoria Soldera, Natasha B Leighl
Despite advances in molecular characterization and lung cancer treatment in recent years, treatment options for patients diagnosed with squamous cell carcinoma of the lung (SCC) remain limited as actionable mutations are rarely detected in this subtype. This article reviews potential molecular targets and associated novel agents for the treatment of advanced SCC in the era of personalized medicine. Elements of various pathways including epidermal growth factor receptor, PI3KCA, fibroblast growth factor receptor, retinoblastoma, cyclin-dependent kinases, discoidin domain receptor tyrosine kinase 2, and mesenchymal-to-epithelial transition may play pivotal roles in the development of SCC and are under investigation for drug development...
2017: Frontiers in Oncology
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/28337325/tetrahydroisoquinoline-7-carboxamide-derivatives-as-new-selective-discoidin-domain-receptor-1-ddr1-inhibitors
#3
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/28270508/discoidin-domain-receptor-2-mediates-collagen-induced-activation-of-membrane-type-1-matrix-metalloproteinase-in-human-fibroblasts
#4
Iwona Majkowska, Yasuyuki Shitomi, Noriko Ito, Nathanael S Gray, Yoshifumi Itoh
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-bound MMP that is highly expressed in cells with invading capacity, including fibroblasts and invasive cancer cells. However, pathways of MT1-MMP up-regulation are not clearly understood. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it up-regulates both MT1-MMP gene and functions in various cell types. However, the mechanisms of collagen-mediated MT1-MMP activation and its physiological relevance are not known...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28199848/discoidin-domain-receptor-1-mediates-myosin-dependent-collagen-contraction
#5
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
#6
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/28161936/prevalence-of-mutations-in-discoidin-domain-containing-receptor-tyrosine-kinase-2-ddr2-in-squamous-cell-lung-cancers-in-korean-patients
#7
Mi-Sook Lee, Eun Ah Jung, Sung Bin An, Yu Jin Kim, Doo-Yi Oh, Ji-Young Song, Sang-Won Um, Joungho Han, Yoon-La Choi
Purpose: The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer. Materials and Methods: We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination...
January 25, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28147276/mesenchymal-stem-cell-induced-ddr2-mediates-stromal-breast-cancer-interactions-and-metastasis-growth
#8
Maria E Gonzalez, Emily E Martin, Talha Anwar, Caroline Arellano-Garcia, Natasha Medhora, Arjun Lama, Yu-Chih Chen, Kevin S Tanager, Euisik Yoon, Kelley M Kidwell, Chunxi Ge, Renny T Franceschi, Celina G Kleer
Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28143619/discoidin-domain-receptor-1-activity-drives-an-aggressive-phenotype-in-gastric-carcinoma
#9
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/28106549/the-multimerization-state-of%C3%A2-the%C3%A2-amyloid-%C3%AE-42-amyloid-peptide-governs-its-interaction-network-with%C3%A2-the%C3%A2-extracellular-matrix
#10
Romain Salza, Claire Lethias, Sylvie Ricard-Blum
The goals of this work were i) to identify the interactions of amyloid-β (Aβ)42 under monomeric, oligomeric, and fibrillar forms with the extracellular matrix (ECM) and receptors, ii) to determine the influence of Aβ42 supramolecular organization on these interactions, and iii) to identify the molecular functions, biological processes, and pathways targeted by Aβ42 in the ECM. The ECM and cell surface partners of Aβ42 and its supramolecular forms were identified with protein and glycosaminoglycan (GAG) arrays (81 molecules in triplicate) probed by surface plasmon resonance imaging...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28046999/su-f-sps-08-measuring-the-interaction-of-ddr-cell-receptors-and-extracellular-matrix-collagen-in-prostate-cells
#11
J Dong, A Sarkar, A Suhail, R Fridman, P Hoffmann
PURPOSE: Discoidin domain receptors (DDR) have recently been recognized as important players in cancer progression. DDRs are cell receptors that interact with collagen, an extracellular matrix (ECM) protein. However the detailed mechanism of their interaction is unclear. Here we attempted to examine their interaction in terms of structural (surface topography), mechanical (rupture force), and kinetic (binding probability) information on the single molecular scale with the use of atomic force microscopy (AFM)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/27984580/the-c-elegans-discoidin-domain-receptor-ddr-2-modulates-the-met-like-rtk-jnk-signaling-pathway-in-axon-regeneration
#12
Naoki Hisamoto, Yuki Nagamori, Tatsuhiro Shimizu, Strahil I Pastuhov, Kunihiro Matsumoto
The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, initiation of axon regeneration is positively regulated by SVH-2 Met-like growth factor receptor tyrosine kinase (RTK) signaling through the JNK MAPK pathway. Here we show that SVH-4/DDR-2, an RTK containing a discoidin domain that is activated by collagen, and EMB-9 collagen type IV regulate the regeneration of neurons following axon injury...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27915093/discoidin-domain-receptor-1-kinase-activity-is-required-for-regulating-collagen-iv-synthesis
#13
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
#14
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/27824116/ddr1-promotes-e-cadherin-stability-via-inhibition-of-integrin-%C3%AE-1-src-activation-mediated-e-cadherin-endocytosis
#15
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/27793038/ddr2-overexpression-in-urothelial-carcinoma-indicates-an-unfavorable-prognosis-a-large-cohort-study
#16
Meng-Chen Tsai, Wei-Ming Li, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Hsin-Chih Yeh, Ti-Chun Chan, Peir-In Liang, Bi-Wen Yeh, Wen-Jeng Wu, Sher-Wei Lim, Chien-Feng Li
The migration ability of urothelial carcinoma corresponding to dismal prognosis had not been fully investigated. The interaction of extracellular collagen with a unique transmembrane receptor tyrosine kinase, Discoidin domain receptor 2 (DDR2), was selected by data mining. We arranged real-time reverse transcription polymerase chain reaction assays to evaluate the transcript levels in 26 urinary tract urothelial carcinoma and 26 urinary bladder urothelial carcinoma specimens, showing significantly increase corresponding to advanced primary stage (p = 0...
November 29, 2016: Oncotarget
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/27703433/corrigendum-discoidin-domain-receptors-potential-actors-and-targets-in-cancer
#18
Hassan Rammal, Charles Saby, Kevin Magnien, Laurence Van-Gulick, Roselyne Garnotel, Emilie Buache, Hassan El Btaouri, Pierre Jeannesson, Hamid Morjani
[This corrects the article on p. 55 in vol. 7, PMID: 27014069.].
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27640147/discoidin-domain-receptor-2-as-a-potential-therapeutic-target-for-development-of-disease-modifying-osteoarthritis-drugs
#19
Lauren B Manning, Yefu Li, Nithya S Chickmagalur, Xiaolong Li, Lin Xu
Osteoarthritis (OA) is the most common form of arthritis disorders, but the identification of therapeutic targets to effectively prevent OA has been increasingly difficult. The goal of this investigation is to provide experimental evidence that discoidin domain receptor 2 (DDR2) may be an ideal target for the development of disease-modifying OA drugs. Ddr2 was conditionally deleted from articular cartilage of adult mouse knee joints. Aggrecan-CreERT2;floxed Ddr2 mice, which were generated by crossing Aggrecan-CreERT2 mice with floxed Ddr2 mice, then received tamoxifen injections at the age of 8 weeks...
September 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27634844/retraction-hyperbaric-oxygen-activates-discoidin-domain-receptor-2-via-tumour-necrosis-factor-%C3%AE-and-the-p38-mapk-pathway-to-increase-vascular-smooth-muscle-cell-migration-through-matrix-metalloproteinase-2
#20
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