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https://www.readbyqxmd.com/read/29733741/age-related-modifications-of-type-i-collagen-impair-ddr1-induced-apoptosis-in-non-invasive-breast-carcinoma-cells
#1
Saby Charles, Rammal Hassan, Magnien Kevin, Buache Emilie, Brassart-Pasco Sylvie, Van-Gulick Laurence, Jeannesson Pierre, Maquoi Erik, Morjani Hamid
Type I collagen and DDR1 axis has been described to decrease cell proliferation and to initiate apoptosis in non-invasive breast carcinoma in three-dimensional cell culture matrices. Moreover, MT1-MMP down-regulates these effects. Here, we address the effect of type I collagen aging and MT1-MMP expression on cell proliferation suppression and induced-apoptosis in non-invasive MCF-7 and ZR-75-1 breast carcinoma. We provide evidence for a decrease in cell growth and an increase in apoptosis in the presence of adult collagen when compared to old collagen...
May 7, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29701112/multitasking-discoidin-domain-receptors-are-involved-in-several-and-specific-hallmarks-of-cancer
#2
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/29616590/ddr1-and-ddr2-physical-interaction-leads-to-signaling-interconnection-but-with-possible-distinct-functions
#3
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
#4
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/29547756/silencing-of-discoidin-domain-receptor-1-ddr1-concurrently-inhibits-multiple-steps-of-metastasis-cascade-in-gastric-cancer
#5
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/29513135/mechanical-signaling-through-the-discoidin-domain-receptor-1-plays-a-central-role-in-tissue-fibrosis
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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/29438985/inhibition-of-ddr1-bcr-signalling-by-nilotinib-as-a-new-therapeutic-strategy-for-metastatic-colorectal-cancer
#12
Maya Jeitany, Cédric Leroy, Priscillia Tosti, Marie Lafitte, Jordy Le Guet, Valérie Simon, Debora Bonenfant, Bruno Robert, Fanny Grillet, Caroline Mollevi, Safia El Messaoudi, Amaëlle Otandault, Lucile Canterel-Thouennon, Muriel Busson, Alain R Thierry, Pierre Martineau, Julie Pannequin, Serge Roche, Audrey Sirvent
The clinical management of metastatic colorectal cancer (mCRC) faces major challenges. Here, we show that nilotinib, a clinically approved drug for chronic myeloid leukaemia, strongly inhibits human CRC cell invasion in vitro and reduces their metastatic potential in intrasplenic tumour mouse models. Nilotinib acts by inhibiting the kinase activity of DDR1, a receptor tyrosine kinase for collagens, which we identified as a RAS-independent inducer of CRC metastasis. Using quantitative phosphoproteomics, we identified BCR as a new DDR1 substrate and demonstrated that nilotinib prevents DDR1-mediated BCR phosphorylation on Tyr177, which is important for maintaining β-catenin transcriptional activity necessary for tumour cell invasion...
April 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29429150/mir-199a-b-5p-inhibits-lymphangiogenesis-by-targeting-discoidin-domain-receptor-1-in-corneal-injury
#13
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/29367920/the-pronounced-high-expression-of-discoidin-domain-receptor-2-in-human-interstitial-lung-diseases
#14
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
https://www.readbyqxmd.com/read/29312631/proteomic-approach-toward-determining-the-molecular-background-of-pazopanib-resistance-in-synovial-sarcoma
#15
Zhiwei Qiao, Kumiko Shiozawa, Tadashi Kondo
Pazopanib, a multitarget tyrosine kinase (TK) inhibitor, has been approved for treatment of soft tissue sarcoma. Elucidation of the molecular background of pazopanib resistance should lead to improved clinical outcomes in sarcomas; accordingly, we investigated this in synovial sarcoma using a proteomic approach. Pazopanib sensitivity was examined in four synovial sarcoma cell lines: SYO-1, HS-SYII, 1273/99, and YaFuSS. The 1273/99 cell line showed significantly higher IC50 values than the others for pazopanib...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298894/tumor-extrinsic-discoidin-domain-receptor-1-promotes-mammary-tumor-growth-by-regulating-adipose-stromal-interleukin-6-production-in-mice
#16
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 communication 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 the stroma of breast tumors are associated with poor patient outcome, a causal role for tumor-extrinsic DDR1 in cancer promotion remains unclear. 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...
February 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29259095/when-e-cadherin-is-away-centrosomes-can-play
#17
Diana Vargas-Hurtado, Renata Basto
Centrosome clustering is a process frequently used by cancer cells with extra centrosomes to avoid multipolar divisions. How cell-intrinsic properties influence clustering is not entirely known. In this issue, Rhys et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201704102) report an unexpected link between clustering capacity and cortical contractility through E-cadherin and DDR1 proteins.
January 2, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29039472/e2f1-silencing-inhibits-migration-and-invasion-of-osteosarcoma-cells-via-regulating-ddr1-expression
#18
Zhaofeng Wang, Xianjie Sun, Yi Bao, Juanfen Mo, Hengchao Du, Jichao Hu, Xingen Zhang
In the present study, knockdown of E2F1 impaired the migration and invasion of osteosarcoma cells. Further analysis showed that E2F1 knockdown decreased the expression of discoidin domain receptor 1 (DDR1) which plays a crucial role in many fundamental processes such as cell differentiation, adhesion, migration and invasion. Luciferase and ChIP assays confirmed that E2F1 silencing attenuated the expression of DDR1 through disrupting E2F1-mediated transcription of DDR1 in osteosarcoma cells. Similarly with the effect of E2F1 silencing, DDR1 knockdown weakened the migratory and invasive capabilities of osteosarcoma cells; while overexpression of DDR1 resulted in a significant increase of cell motility and invasiveness, even after knocking down E2F1...
December 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28952134/molecular-mechanisms-underlying-gliomas-and-glioblastoma-pathogenesis-revealed-by-bioinformatics-analysis-of-microarray-data
#19
Basavaraj Vastrad, Chanabasayya Vastrad, Ashok Godavarthi, Raghu Chandrashekar
The aim of this study was to identify key genes associated with gliomas and glioblastoma and to explore the related signaling pathways. Gene expression profiles of three glioma stem cell line samples, three normal astrocyte samples, three astrocyte overexpressing 4 iPSC-inducing and oncogenic factors (myc(T58A), OCT-4, p53DD, and H-Ras(G12V)) samples, three astrocyte overexpressing 7 iPSC-inducing and oncogenic factors (OCT4, H-Ras(G12V), myc(T58A), p53DD, cyclin D1, CDK4(RC24) and hTERT) samples and three glioblastoma cell line samples were downloaded from the ArrayExpress database (accession: E-MTAB-4771)...
September 26, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28904079/ascorbic-acid-promotes-a-tgf%C3%AE-1-induced-myofibroblast-phenotype-switch
#20
Bram Piersma, Olaf Y Wouters, Saskia de Rond, Miriam Boersema, Rutger A F Gjaltema, Ruud A Bank
l-Ascorbic acid (AA), generally known as vitamin C, is a crucial cofactor for a variety of enzymes, including prolyl-3-hydroxylase (P3H), prolyl-4-hydroxylase (P4H), and lysyl hydroxylase (LH)-mediated collagen maturation. Here, we investigated whether AA has additional functions in the regulation of the myofibroblast phenotype, besides its function in collagen biosynthesis. We found that AA positively influences TGFβ1-induced expression of COL1A1, ACTA2, and COL4A1 Moreover, we demonstrated that AA promotes αSMA stress fiber formation as well as the synthesis and deposition of collagens type I and IV Additionally, AA amplified the contractile phenotype of the myofibroblasts, as seen by increased contraction of a 3D collagen lattice...
September 2017: Physiological Reports
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