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Discoidin domain receptor

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https://www.readbyqxmd.com/read/29769618/inhibitor-of-apoptosis-proteins-iaps-mediate-collagen-type-xi-alpha-1-driven-cisplatin-resistance-in-ovarian-cancer
#1
Miran Rada, Sameera Nallanthighal, Jennifer Cha, Kerry Ryan, Jessica Sage, Catherine Eldred, Maria Ullo, Sandra Orsulic, Dong-Joo Cheon
Although, cisplatin resistance is a major challenge in the treatment of ovarian cancer, the precise mechanisms underlying cisplatin resistance are not fully understood. Collagen type XI alpha 1 (COL11A1), a gene encoding a minor fibrillar collagen of the extracellular matrix, is identified as one of the most upregulated genes in cisplatin-resistant ovarian cancer and recurrent ovarian cancer. However, the exact functions of COL11A1 in cisplatin resistance are unknown. Here we demonstrate that COL11A1 binds to integrin α1β1 and discoidin domain receptor 2 (DDR2) and activates downstream signaling pathways to inhibit cisplatin-induced apoptosis in ovarian cancer cells...
May 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29709482/spatial-localisation-of-discoidin-domain-receptor-2-ddr2-signalling-is-dependent-on-its-collagen-binding-and-kinase-activity
#2
Maciej T Luczynski, Peter T Harrison, Nadia Lima, Lukas Krasny, Angela Paul, Paul H Huang
Discoidin Domain Receptor 2 (DDR2) is a collagen-binding receptor tyrosine kinase that initiates delayed and sustained tyrosine phosphorylation signalling. To understand the molecular basis of this unique phosphorylation profile, here we utilise fluorescence microscopy to map the spatiotemporal localisation of DDR2 and tyrosine phosphorylated proteins upon stimulation with collagen. We show that cellular phosphorylated proteins are localised to the interface where DDR2 is in contact with collagen and not in the early endosomes or lysosomes...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29701112/multitasking-discoidin-domain-receptors-are-involved-in-several-and-specific-hallmarks-of-cancer
#3
Elodie Henriet, Margaux Sala, Aya Abou Hammoud, Adjanie Tuariihionoa, Julie Di Martino, Manon Ros, Frédéric Saltel
Discoidin domain receptors, DDR1 and DDR2, are two members of collagen receptor family that belong to tyrosine kinase receptor subgroup. Unlike other matrix receptor-like integrins, these collagen receptors have not been extensively studied. However, more and more studies are focusing on their involvement in cancer. These two receptors are present in several subcellular localizations such as intercellular junction or along type I collagen fibers. Consequently, they are involved in multiple cellular functions, for instance, cell cohesion, proliferation, adhesion, migration and invasion...
April 27, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29671358/discoidin-domain-receptors-microenvironment-sensors-that-promote-cellular-migration-and-invasion
#4
Yoshifumi Itoh
Extracellular matrix (ECM) provides cells scaffolding for cell migration and microenvironment for various cellular functions. Collagens are major ECM components in tissue and discoidin domain receptors (DDRs) are receptor tyrosine kinases (RTK) that recognise fibrillar collagens. Unlike other RTK, their ligands are solid ECM the that are abundantly present in the pericellular environment in various tissue, and thus its activation and regulations are unique amongst RTK family. It is emerging that DDRs may be the sensors that monitor and detects changes in ECM microenvironment and determines the cellular fates upon tissue injuries...
April 19, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29656147/liver-fibrosis-direct-antifibrotic-agents-and-targeted-therapies
#5
REVIEW
Detlef Schuppan, Muhammad Ashfaq-Khan, Ai Ting Yang, Yong Ook Kim
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases...
April 12, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29652518/discoidin-domain-receptor-2-signaling-regulates-fibroblast-apoptosis-through-pdk1-akt
#6
Shijing Jia, Manisha Agarwal, Jibing Yang, Jeffrey C Horowitz, Eric S White, Kevin K Kim
Progressive fibrosis is a complication of many chronic diseases and collectively, organ fibrosis is the leading cause of death in the US. Fibrosis is characterized by accumulation of activated fibroblasts and excessive deposition of extracellular matrix proteins, especially type I collagen. Extensive research has supported a role for matrix signaling in propagating fibrosis but type I collagen itself is often considered an end product of fibrosis rather than an important regulator of continued collagen deposition...
April 13, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29616590/ddr1-and-ddr2-physical-interaction-leads-to-signaling-interconnection-but-with-possible-distinct-functions
#7
Coralie Croissant, Adjanie Tuariihionoa, Marion Bacou, Wilfried Souleyreau, Margaux Sala, Elodie Henriet, Andreas Bikvalvi, Frederic Saltel, Patrick Auguste
Discoidin domain receptors 1 and 2 (DDR1 and DDR2) are members of the tyrosine kinase receptors activated after binding with collagen. DDRs are implicated in numerous physiological and pathological functions such as proliferation, adhesion and migration. Little is known about the expressions of the two receptors in normal and cancer cells and most of studies focus only on one receptor. Western blot analysis of DDR1 and DDR2 expression in different tumor cell lines shows an absence of high co-expression of the two receptors suggesting a deleterious effect of their presence at high amount...
April 4, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29559654/complement-c1q-stimulates-the-progression-of-hepatocellular-tumor-through-the-activation-of-discoidin-domain-receptor-1
#8
Ji-Hyun Lee, Barun Poudel, Hyeon-Hui Ki, Sarmila Nepali, Young-Mi Lee, Jeon-Soo Shin, Dae-Ki Kim
C1q is known to perform several functions in addition to the role it plays in complement activation. C1q contains a collagen-like portion and DDR1 (discoidin domain receptor 1) is a well-known collagen receptor. Accordingly, we hypothesized C1q might be a novel ligand of DDR1. This study shows for the first time C1q directly induces the activation and upregulation of DDR1, and that this leads to enhanced migration and invasion of HepG2 cells. In addition, C1q was found to induce the activations of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/Akt signaling, and to increase the expressions of matrix metalloproteinases (MMP2 and 9)...
March 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29550247/the-transmembrane-collagen-col-99-guides-longitudinally-extending-axons-in-c-elegans
#9
Jesse Taylor, Thomas Unsoeld, Harald Hutter
We have identified the transmembrane collagen, COL-99, in a genetic screen for novel genes involved in axon guidance in the nematode C. elegans. COL-99 is similar to transmembrane collagens type XIII, XXIII and XXV in vertebrates. col-99 mutants exhibit guidance defects in axons extending along the major longitudinal axon tracts, most prominently the left ventral nerve cord (VNC). COL-99 is expressed in the hypodermis during the time of axon outgrowth. We provide evidence that a furin cleavage site in COL-99 is essential for function, suggesting that COL-99 is released from the cells producing it...
March 15, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29547756/silencing-of-discoidin-domain-receptor-1-ddr1-concurrently-inhibits-multiple-steps-of-metastasis-cascade-in-gastric-cancer
#10
Ryo Yuge, Yasuhiko Kitadai, Hidehiko Takigawa, Toshikatsu Naito, Naohide Oue, Wataru Yasui, Shinji Tanaka, Kazuaki Chayama
Accumulating evidence suggests that a unique set of receptor tyrosine kinases, known as discoidin domain receptors (DDRs), plays a role in cancer progression by interacting with the surrounding collagen matrix. In this study, we investigated the expression and role of DDR1 in human gastric cancer metastasis. Proliferation, migration, invasion, and tube formation assays were conducted in DDR1-expressing MKN74 gastric cancer cells and corresponding DDR1-silenced cells. The effects of DDR1 on tumor growth and metastasis were examined in orthotopically implanted and experimental liver metastasis models in nude mice...
March 13, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29519912/correction-discoidin-domain-receptor-2-deficiency-predisposes-hepatic-tissue-to-colon-carcinoma-metastasis
#11
(no author information available yet)
No abstract text is available yet for this article.
April 2018: Gut
https://www.readbyqxmd.com/read/29513135/mechanical-signaling-through-the-discoidin-domain-receptor-1-plays-a-central-role-in-tissue-fibrosis
#12
Nuno M Coelho, Christopher A McCulloch
The preservation of tissue and organ architecture and function depends on tightly regulated interactions of cells with the extracellular matrix (ECM). These interactions are maintained in a dynamic equilibrium that balances intracellular, myosin-generated tension with extracellular resistance conferred by the mechanical properties of the extracellular matrix. Disturbances of this equilibrium can lead to the development of fibrotic lesions that are associated with a wide repertoire of high prevalence diseases including obstructive cardiovascular diseases, muscular dystrophy and cancer...
March 26, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29505315/a-putative-role-for-discoidin-domain-receptor-1-in-cancer-chemoresistance
#13
Chiara Ambrogio, Elodie Darbo, Sam W Lee, David Santamaría
The Discoidin Domain Receptor 1 (DDR1) receptor tyrosine kinase performs pleiotropic functions in the control of cell adhesion, proliferation, survival, migration, and invasion. Aberrant DDR1 function as a consequence of either mutations or increased expression has been associated with various human diseases including cancer. Pharmacological inhibition of DDR1 results in significant therapeutic benefit in several pre-clinical cancer models. Here, we discuss the potential implication of DDR1-dependent pro-survival functions in the development of cancer resistance to chemotherapeutic regimens and speculate on the molecular mechanisms that might mediate such important feature...
April 3, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29486622/a-novel-functional-crosstalk-between-ddr1-and-the-igf-axis-and-its-relevance-for-breast-cancer
#14
Antonino Belfiore, Roberta Malaguarnera, Maria Luisa Nicolosi, Rosamaria Lappano, Marco Ragusa, Andrea Morrione, Veronica Vella
In the last decades increasing importance has been attributed to the Insulin/Insulin-like Growth Factor signaling (IIGFs) in cancer development, progression and resistance to therapy. In fact, IIGFs is often deregulated in cancer. In particular, the mitogenic insulin receptor isoform A (IR-A) and the insulin-like growth factor receptor (IGF-1R) are frequently overexpressed in cancer together with their cognate ligands IGF-1 and IGF-2. Recently, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein...
March 23, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29483153/discoidin-domain-receptor-1-ddr1-ablation-promotes-tissue-fibrosis-and-hypoxia-to-induce-aggressive-basal-like-breast-cancers
#15
Ken Takai, Allison P Drain, Devon A Lawson, Laurie E Littlepage, Marcela Karpuj, Kai Kessenbrock, Annie Le, Kenichi Inoue, Valerie M Weaver, Zena Werb
The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression is associated with worse relapse-free survival, reflecting its controversial role in cancer progression. We detected DDR1 on luminal cells but not on myoepithelial cells of DDR1+/+ mice. We found that DDR1 loss compromises cell adhesion, consistent with data that older DDR1-/- mammary glands had more basal/myoepithelial cells. Basal cells isolated from older mice exerted higher traction forces than the luminal cells, in agreement with increased mammary branches observed in older DDR1-/- mice and higher branching by their isolated organoids...
February 1, 2018: Genes & Development
https://www.readbyqxmd.com/read/29467865/discoidin-domain-receptor-1-new-star-in-cancer-targeted-therapy-and-its-complex-role-in-breast-carcinoma
#16
Hui Jing, Jingyuan Song, Junnian Zheng
Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by various types of collagens that performs a critical role in cell attachment, migration, survival and proliferation. The functions of DDR1 in various types of tumor have been studied extensively. However, in breast carcinoma, the roles of collagen-evoked DDR1 remain ill defined. Although a number of studies have reported that DDR1 promotes apoptosis and inhibits migration in breast carcinoma, it has also been reported to be associated with tumor cell survival, chemoresistance to genotoxic drugs and the facilitation of invasion...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29455614/ddr1-a-major-player-in-renal-diseases
#17
Aude Dorison, Christos Chantziantoniou
Discoidin Domain Receptor 1 (DDR1) belongs to a family of two non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. DDR1 has been widely studied in different kind of pathologies including chronic kidney diseases (CKD). The aims of this commentary are 1. to review the existing information about DDR1 expression in healthy and diseased kidney, 2. to comment the data highlighting DDR1 as a major actor in CKD, 3. to suggest areas of research which require further investigation to better characterize the signaling pathways regulating DDR1 role in CKD...
February 27, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29429150/mir-199a-b-5p-inhibits-lymphangiogenesis-by-targeting-discoidin-domain-receptor-1-in-corneal-injury
#18
Sooeun Oh, Minkoo Seo, Jun-Sub Choi, Choun-Ki Joo, Suk Kyeong Lee
Discoidin domain receptor 1 (DDR1) is involved in tumorigenesis and angiogenesis. However, its role in lymphangiogenesis has been unknown. Here, we tested whether downregulation of DDR1 expression by miR-199a/b can suppress lymphangiogenesis. We also aimed to identify miRNA target site(s) in the 3' untranslated region (UTR) of DDR1 . Transfection with miR-199a/b-5p mimics reduced expression of DDR1 and tube formation in primary human dermal lymphatic endothelial cells, whereas miR-199a/b-5p inhibitors showed the opposite effects...
February 28, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29382361/trypanosoma-cruzi-activates-mouse-cardiac-fibroblasts-in-vitro-leading-to-fibroblast-myofibroblast-transition-and-increase-in-expression-of-extracellular-matrix-proteins
#19
Laura Lacerda Coelho, Isabela Resende Pereira, Mirian Claudia de Souza Pereira, Liliane Mesquita, Joseli Lannes-Vieira, Daniel Adesse, Luciana Ribeiro Garzoni
BACKGROUND: Cardiac fibrosis is a consequence of chronic chagasic cardiomyopathy (CCC). In other cardiovascular diseases, the protagonist role of fibroblasts in cardiac fibrosis is well established. However, the role of cardiac fibroblasts (CFs) in fibrosis during the CCC is not clear. Here, our aim was to investigate the effect of Trypanosoma cruzi, the etiological agent of Chagas disease on CFs activation. METHODS: Cardiac fibroblasts were purified from primary cultures of mouse embryo cardiac cells...
January 30, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29367920/the-pronounced-high-expression-of-discoidin-domain-receptor-2-in-human-interstitial-lung-diseases
#20
Huan Bian, Xiaowei Nie, Xin Bu, Feng Tian, Libo Yao, Jingyu Chen, Jin Su
The most typical structural feature of human interstitial lung diseases (ILDs) is the accumulation of vast amounts of collagens within the lung interstitium. The membrane receptors that are responsible for recognising collagens and then transducing signals into the cells include four members of the integrin family (α1β1, α2β1, α10β1 and α11β1) and two members of the discoidin domain receptor family (DDR1 and DDR2). However, it remains unknown whether these six collagen receptors similarly contribute to the pathogenesis of fibrotic lung diseases...
January 2018: ERJ Open Research
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