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https://www.readbyqxmd.com/read/29039472/e2f1-silencing-inhibits-migration-and-invasion-of-osteosarcoma-cells-via-regulating-ddr1-expression
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28887161/loss-of-discoidin-domain-receptor-1-ddr1-via-cpg-methylation-during-emt-in-epithelial-ovarian-cancer
#4
Vin Yee Chung, Tuan Zea Tan, Rui-Lan Huang, Hung-Cheng Lai, Ruby Yun-Ju Huang
Epithelial ovarian cancer (EOC) can be stratified according to the stages of epithelial-mesenchymal transition (EMT). Here, we aim to identify tyrosine kinases (TKs) in EOC that correlate with the EMT subtypes. By gene expression microarray, we analyzed the expression levels of tyrosine kinases in EOC cell lines in correlation with EMT. Among the candidate TKs identified, DDR1 was expressed mainly in EOC cells with an Epithelial phenotype. Its expression was validated by qPCR, ELISA and western blotting. Using Infinium HumanMethylation27K BeadChip array and pyrosequencing, we further analyzed the CpG methylation levels at the DDR1 promoter in EOC cells and found that the CpG methylation levels of DDR1 promoter correlated negatively with the expression of DDR1 along the EMT spectrum...
November 30, 2017: Gene
https://www.readbyqxmd.com/read/28864681/inhibition-of-discoidin-domain-receptor-1-reduces-collagen-mediated-tumorigenicity-in-pancreatic-ductal-adenocarcinoma
#5
Kristina Y Aguilera, Huocong Huang, Wenting Du, Moriah M Hagopian, Zhen Wang, Stefan Hinz, Tae Hyun Hwang, Huamin Wang, Jason B Fleming, Diego H Castrillon, Xiaomei Ren, Ke Ding, Rolf A Brekken
The extracellular matrix (ECM), a principal component of pancreatic ductal adenocarcinoma (PDA), is rich in fibrillar collagens that facilitate tumor cell survival and chemoresistance. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that specifically binds fibrillar collagens and has been implicated in promoting cell proliferation, migration, adhesion, ECM remodeling, and response to growth factors. We found that collagen-induced activation of DDR1 stimulated protumorigenic signaling through protein tyrosine kinase 2 (PYK2) and pseudopodium-enriched atypical kinase 1 (PEAK1) in pancreatic cancer cells...
November 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28863860/discoidin-domain-receptor-inhibition-reduces-neuropathology-and-attenuates-inflammation-in-neurodegeneration-models
#6
Michaeline Hebron, Margo Peyton, Xiaoguang Liu, Xiaokong Gao, Ruochong Wang, Irina Lonskaya, Charbel E-H Moussa
The role of cell surface tyrosine kinase collagen-activated receptors known as discoidin domain receptors (DDRs) is unknown in neurodegenerative diseases. We detect up-regulation in DDRs level in post-mortem Alzheimer and Parkinson brains. Lentiviral shRNA knockdown of DDR1 and DDR2 reduces the levels of α-synuclein, tau, and β-amyloid and prevents cell loss in vivo and in vitro. DDR1 and DDR2 knockdown alters brain immunity and significantly reduces the level of triggering receptor expressed on myeloid cells (TREM)-2 and microglia...
October 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28821283/gene-expression-profiling-of-idiopathic-interstitial-pneumonias-iips-identification-of-potential-diagnostic-markers-and-therapeutic-targets
#7
Yasushi Horimasu, Nobuhisa Ishikawa, Masaya Taniwaki, Kakuhiro Yamaguchi, Kosuke Hamai, Hiroshi Iwamoto, Shinichiro Ohshimo, Hironobu Hamada, Noboru Hattori, Morihito Okada, Koji Arihiro, Yuji Ohtsuki, Nobuoki Kohno
BACKGROUND: Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This study aims to investigate the genetic backgrounds of IIP through gene expression profiling and pathway analysis, and to identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic targets. METHODS: RNA extracted from lung specimens of 12 patients with chronic fibrosing IIP was profiled using Illumina Human WG-6 v3 BeadChips, and Ingenuity Pathway Analysis was performed to identify altered functional and canonical signaling pathways...
August 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28743276/suppressing-mir-199a-3p-by-promoter-methylation-contributes-to-tumor-aggressiveness-and-cisplatin-resistance-of-ovarian-cancer-through-promoting-ddr1-expression
#8
Yuao Deng, Fang Zhao, Liu Hui, Xiuyun Li, Danyu Zhang, Wang Lin, Zhiqiang Chen, Yingxia Ning
BACKGROUND: Discoidin Domain Receptor 1 (DDR1) belongs to the family of collagen receptor tyrosine kinases that confers the progression of various cancers. Aberrant expression of DDR1 was detected in several human cancers including ovarian cancer, which had been shown to increase the migration and invasion of tumor cells. However, the precise mechanisms underlying the abnormal expression of DDR1 in ovarian cancer has not been well investigated in previous studies. RESULTS: In this work, a negative correlation between DDR1 and a tumor suppressor miRNA, miR-199a-3p, was observed in ovarian cancer tissues...
July 25, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28743124/the-role-of-discoidin-domain-receptor-1-in-inflammation-fibrosis-and-renal-disease
#9
Aude Dorison, Jean-Claude Dussaule, Christos Chatziantoniou
Discoidin domain receptors (DDRs) are a family of 2 non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. They are mainly expressed during embryonic development and their role during adulthood is very limited. DDR1 has been widely studied in several types of cancers, in atherosclerosis and fibrosis, but also in chronic kidney disease (CKD). This review focuses on the role of DDR1 in chronic nephropathies and on the effect of its deletion in the pathological processes involved in renal disease progression...
July 26, 2017: Nephron
https://www.readbyqxmd.com/read/28723646/collagen-type-1-promotes-survival-of-human-breast-cancer-cells-by-overexpressing-kv10-1-potassium-and-orai1-calcium-channels-through-ddr1-dependent-pathway
#10
Mehdi Badaoui, Cloé Mimsy-Julienne, Charles Saby, Laurence Van Gulick, Marta Peretti, Pierre Jeannesson, Hamid Morjani, Halima Ouadid-Ahidouch
Collagen type 1 is among the tumor microenvironment (TM) factors, that regulates proliferation, survival, migration and invasion. Ion channels are key players in interactions between tumor cells and TM. Kv10.1 has been shown to play an essential role in breast cancer cell proliferation and migration by permitting Ca2+ influx notably via Orai1. Here, we show that human breast cancer (BC) cells growing, in culture media completely devoid of the serum and seeded on collagen 1 coating, exhibited less apoptotic rate and a decrease in Bax expression when compared to those grown on plastic...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718798/co-expression-network-and-pathway-analyses-reveal-important-modules-of-mirnas-regulating-milk-yield-and-component-traits
#11
Duy N Do, Pier-Luc Dudemaine, Ran Li, Eveline M Ibeagha-Awemu
Co-expression network analyses provide insights into the molecular interactions underlying complex traits and diseases. In this study, co-expression network analysis was performed to detect expression patterns (modules or clusters) of microRNAs (miRNAs) during lactation, and to identify miRNA regulatory mechanisms for milk yield and component traits (fat, protein, somatic cell count (SCC), lactose, and milk urea nitrogen (MUN)) via miRNA target gene enrichment analysis. miRNA expression (713 miRNAs), and milk yield and components (Fat%, Protein%, lactose, SCC, MUN) data of nine cows at each of six different time points (day 30 (D30), D70, D130, D170, D230 and D290) of an entire lactation curve were used...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28691208/transcriptomic-profile-analysis-of-mouse-neural-tube-development-by-rna-seq
#12
Juan Yu, Jianbing Mu, Qian Guo, Lihong Yang, Juan Zhang, Zhizhen Liu, Baofeng Yu, Ting Zhang, Jun Xie
The neural tube is the primordium of the central nervous system (CNS) in which its development is not entirely clear. Understanding the cellular and molecular basis of neural tube development could, therefore, provide vital clues to the mechanism of neural tube defects (NTDs). Here, we investigated the gene expression profiles of three different time points (embryonic day (E) 8.5, 9.5 and 10.5) of mouse neural tube by using RNA-seq approach. About 391 differentially expressed genes (DEGs) were screened during mouse neural tube development, including 45 DEGs involved in CNS development, among which Bmp2, Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles...
September 2017: IUBMB Life
https://www.readbyqxmd.com/read/28615674/meta-analysis-of-genome-wide-snp-and-pathway-based-associations-for-facets-of-neuroticism
#13
Song E Kim, Han-Na Kim, Yeo-Jun Yun, Seong Gu Heo, Juhee Cho, Min-Jung Kwon, Yoosoo Chang, Seungho Ryu, Hocheol Shin, Chol Shin, Nam H Cho, Yeon Ah Sung, Hyung-Lae Kim
Neuroticism is a heritable personality trait that is comprised of distinct sub-factors, or facets. Sub-factors of neuroticism are linked to different emotional states or psychiatric symptoms and studying the genetic variants associated with these facets may help reveal the biological mechanisms underlying psychiatric disorders. In the present study, a meta-analysis of genome-wide association studies for six facets of neuroticism was performed in 5584 participants from three cohorts. Additionally, a Gene Set Enrichment Analysis was conducted to find biological pathways associated with each facet...
October 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28605388/2d-and-3d-matrices-to-study-linear-invadosome-formation-and-activity
#14
Julie Di Martino, Elodie Henriet, Zakaria Ezzoukhry, Chandrani Mondal, Jose Javier Bravo-Cordero, Violaine Moreau, Frederic Saltel
Cell adhesion, migration, and invasion are involved in many physiological and pathological processes. For example, during metastasis formation, tumor cells have to cross anatomical barriers to invade and migrate through the surrounding tissue in order to reach blood or lymphatic vessels. This requires the interaction between cells and the extracellular matrix (ECM). At the cellular level, many cells, including the majority of cancer cells, are able to form invadosomes, which are F-actin-based structures capable of degrading ECM...
June 2, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28591735/discoidin-domain-receptor-1-modulates-insulin-receptor-signaling-and-biological-responses-in-breast-cancer-cells
#15
Veronica Vella, Roberta Malaguarnera, Maria Luisa Nicolosi, Chiara Palladino, Cristina Spoleti, Michele Massimino, Paolo Vigneri, Michele Purrello, Marco Ragusa, Andrea Morrione, Antonino Belfiore
The fetal isoform A of the insulin receptor (IR-A) is frequently overexpressed in a variety of malignancies including breast cancer. IR overexpression has a recognized role in cancer progression and resistance to anticancer therapies. In particular, IR-A has a peculiar mitogenic potential and is activated not only by insulin but also by IGF-2. Previously, we identified discoidin domain receptor 1 (DDR1) as a new IR-A interacting protein. DDR1, a non-integrin collagen tyrosine kinase receptor, is overexpressed in several malignancies and plays a role in cancer progression and metastasis...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590245/collagen-induces-activation-of-ddr1-through-lateral-dimer-association-and-phosphorylation-between-dimers
#16
Victoria Juskaite, David S Corcoran, Birgit Leitinger
The collagen-binding receptor tyrosine kinase DDR1 (discoidin domain receptor 1) is a drug target for a wide range of human diseases, but the molecular mechanism of DDR1 activation is poorly defined. Here we co-expressed different types of signalling-incompetent DDR1 mutants ('receiver') with functional DDR1 ('donor') and demonstrate phosphorylation of receiver DDR1 by donor DDR1 in response to collagen. Making use of enforced covalent DDR1 dimerisation, which does not affect receptor function, we show that receiver dimers are phosphorylated in trans by the donor; this process requires the kinase activity of the donor but not that of the receiver...
June 7, 2017: ELife
https://www.readbyqxmd.com/read/28560000/discoidin-domain-receptor-1-activity-drives-an-aggressive-phenotype-in-bladder-cancer
#17
Xin Xie, Wenbin Rui, Wei He, Yuan Shao, Fukang Sun, Wenlong Zhou, Yuxuan Wu, Yu Zhu
Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase which utilizes collagen as a ligand to regulate the interaction between cancer cells and tumor stroma. However, the clinical relevance of DDR1 expression in bladder cancer as well as its molecular regulation have not been previously investigated. Here, we assessed the role of DDR1 in bladder cancer. The DDR1 levels in bladder cancer specimens were examined by Western blot, compared to the paired adhesive normal controls. The effects of DDR1 were explored on both cell migration in bladder cancer cells and tumor growth as xenograft...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28536691/periostin-and-discoidin-domain-receptor-1-new-biomarkers-or-targets-for-therapy-of-renal-disease
#18
REVIEW
Niki Prakoura, Christos Chatziantoniou
Chronic kidney disease (CKD) can be a life-threatening condition, which eventually requires renal replacement therapy through dialysis or transplantation. A lot of effort and resources have been invested the last years in the identification of novel markers of progression and targets for therapy, in order to achieve a more efficient prognosis, diagnosis, and treatment of renal diseases. Using experimental models of renal disease, we identified and studied two promising candidates: periostin, a matricellular protein with high expression in bone and dental tissues, and discoidin domain receptor 1 (DDR1), a transmembrane collagen receptor of the tyrosine kinase family...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28455409/ddr1-receptor-tyrosine-kinase-promotes-prosurvival-pathway-through-notch1-activation
#19
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
#20
REVIEW
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
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