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Discoidin domain receptor

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
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
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
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April 2018: Gut
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 7, 2018: Cell Adhesion & Migration
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...
March 5, 2018: Cell Adhesion & Migration
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...
February 28, 2018: Cell Adhesion & Migration
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 26, 2018: Genes & Development
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
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 19, 2018: Cell Adhesion & Migration
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
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
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
Whitney R Grither, Laura M Divine, Eric H Meller, Daniel J Wilke, Riva A Desai, Andrew J Loza, Peinan Zhao, Anne Lohrey, Gregory D Longmore, Katherine C Fuh
The mesenchymal gene program has been shown to promote the metastatic progression of ovarian cancer; however, specific proteins induced by this program that lead to these metastatic behaviors have not been identified. Using patient derived tumor cells and established human ovarian tumor cell lines, we find that the Epithelial-to-Mesenchymal Transition inducing factor TWIST1 drives expression of discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK) that recognizes fibrillar collagen as ligand...
January 19, 2018: Oncogene
Haruta Mogami, Annavarapu Hari Kishore, R Ann Word
Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth. Recently, extracellular matrix-directed treatment is applied for wound healing. Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel for healing of the prematurely ruptured fetal membranes. Although injection of PBS into the ruptured fetal membranes resulted in 40% closure, injection of collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2 wound healing phenotype were entrapped in the collagen layer...
January 12, 2018: Scientific Reports
Jung Ran Choi, Sang-Baek Koh, Seong Yong Park, Hye Run Kim, Hyojin Lee, Dae Ryong Kang
Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs...
December 2017: Journal of Cancer Prevention
Xiujie Sun, Kshama Gupta, Bogang Wu, Deyi Zhang, Bin Yuan, Xiaowen Zhang, Huai-Chin Chiang, Chi Zhang, Tyler J Curiel, Michelle P Bendeck, Stephen Hursting, Yanfen Hu, Rong Li
Discoidin domain receptor 1 (DDR1) is a collagen receptor that mediates cell communications with the extracellular matrix (ECM). Aberrant expression and activity of DDR1 in tumor cells are known to promote tumor growth. Although elevated DDR1 levels in stroma of breast tumors are associated with poor patient outcome, a causal role for tumor-extrinsic DDR1 in cancer promotion remains unclear, however. Here, we report that murine mammary tumor cells transplanted to syngeneic recipient mice in which Ddr1 has been knocked out (KO) grow less robustly than in WT mice...
January 3, 2018: Journal of Biological Chemistry
Caterina Mancarella, Katia Scotlandi
The insulin-like growth factor (IGF) system has gained substantial interest due to its involvement in regulating cell proliferation, differentiation and survival during anoikis and after conventional and targeted therapies. However, results from clinical trials have been largely disappointing, with only a few but notable exceptions, such as trials targeting sarcomas, especially Ewing sarcoma. This review highlights key studies focusing on IGF signaling in sarcomas, specifically studies underscoring the properties that make this system an attractive therapeutic target, and identifies new relationships that may be exploited...
December 22, 2017: Journal of Molecular Endocrinology
Zhong Liang, Wen-Jun Xie, Ming Zhao, Guo-Ping Cheng, Mei-Juan Wu
The upregulation of discoidin domain receptor tyrosine kinase 2 (DDR2) has been reported to be associated with poor prognosis and metastasis in numerous tumor types by inducing epithelial-mesenchymal transition (EMT); however, the expression profile of DDR2 in papillary thyroid carcinoma (PTC) with local metastasis and the effect of DDR2 on PTC cells remain unknown. The aim of the present study was to investigate the expression levels of DDR2 in tumor tissues of patients with PTC with local metastasis and cell lines and to determine the effect of DDR2 on EMT in PTC cells...
December 2017: Oncology Letters
Keran Jiang, Zhongli Yang, Wenyan Cui, Kunkai Su, Jennie Z Ma, Thomas J Payne, Ming D Li
Introduction: Cigarette smoking is one of the largest causes of preventable death worldwide. This study aimed to identify susceptibility loci for age at smoking initiation (ASI) by performing exome-wide association analysis. Methods: A total of 2,510 smokers of either African-American (AA) or European-American (EA) origin were genotyped and analyzed at both the single nucleotide polymorphism (SNP) and gene levels. After removal of those SNPs with minor allele frequency (<0...
December 5, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
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