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Discoidin domain receptor

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https://www.readbyqxmd.com/read/29330408/collagen-type-1-accelerates-healing-of-ruptured-fetal-membranes
#1
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
https://www.readbyqxmd.com/read/29302581/novel-genetic-associations-between-lung-cancer-and-indoor-radon-exposure
#2
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
https://www.readbyqxmd.com/read/29298894/tumor-extrinsic-discoidin-domain-receptor-1-promotes-mammary-tumor-growth-by-regulatingadipose-stromal-interleukin-6-production-in-mice
#3
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
https://www.readbyqxmd.com/read/29273680/igf-system-in-sarcomas-a-crucial-pathway-with-many-unknowns-to-exploit-for-therapy
#4
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
https://www.readbyqxmd.com/read/29250189/ddr2-facilitates-papillary-thyroid-carcinoma-epithelial-mesenchymal-transition-by-activating-erk2-snail1-pathway
#5
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
https://www.readbyqxmd.com/read/29216386/an-exome-wide-association-study-identifies-new-susceptibility-loci-for-age-of-smoking-initiation-in-african-and-european-american-populations
#6
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
https://www.readbyqxmd.com/read/29129434/mutational-landscape-of-ddr2-gene-in-lung-squamous-cell-carcinoma-using-next-generation-sequencing
#7
Charles Ricordel, Alexandra Lespagnol, Francisco Llamas-Gutierrez, Marie de Tayrac, Mallorie Kerjouan, Alice Fievet, Houda Hamdi-Rozé, Amyrat Aliouat, Benoit Desrues, Jean Mosser, Hervé Léna
BACKGROUND: Lung cancer represents the leading cause of cancer-related death worldwide. Despite great advances in lung cancer management with the recent emergence of molecular targeted therapies for non-squamous non-small-cell lung cancer, no dramatic improvements have been achieved in lung squamous cell carcinoma (SCC). Mutations in discoidin domain receptor 2 (DDR2) gene were recently identified as promising molecular targets in this histology. The aim of this study is to describe the DDR2 mutational landscape of lung SCC and investigate the associated clinical factors...
October 19, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29073363/selective-role-of-discoidin-domain-receptor-2-in-murine-temporomandibular-joint-development-and-aging
#8
C Ge, F Mohamed, A Binrayes, S Kapila, R T Franceschi
Temporomandibular joint (TMJ) disorders are often associated with development of osteoarthritis-like changes in the mandibular condyle. Discoidin domain receptor 2 (DDR2), a collagen receptor preferentially activated by type I and III collagen found in the TMJ and other fibrocartilages, has been associated with TMJ degeneration, but its role in normal joint development has not been previously examined. Using Ddr2 LacZ-tagged mice and immunohistochemistry, we found that DDR2 is preferentially expressed and activated in the articular zone of TMJs but not knee joints...
October 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29039472/e2f1-silencing-inhibits-migration-and-invasion-of-osteosarcoma-cells-via-regulating-ddr1-expression
#9
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/29025973/dynamic-multi-site-phosphorylation-by-fyn-and-abl-drives-the-interaction-between-crkl-and-the-novel-scaffolding-receptors-dcbld1-and-dcbld2
#10
Anna M Schmoker, Jaye L Weinert, Kyle J Kellett, Hannah E Johnson, Ryan M Joy, Marion E Weir, Alicia M Ebert, Bryan A Ballif
Discoidin, CUB, and LCCL Domain-containing (DCBLD) 2 is a neuropilin-like transmembrane scaffolding receptor with known and anticipated roles in vascular remodeling and neuronal positioning. DCBLD2 is also upregulated in several cancers and can drive glioblastomas downstream of activated Epidermal Growth Factor Receptor. While a few studies have shown either a positive or negative role for DCBLD2 in regulating growth factor receptor signaling, little is known about the conserved signaling features of DCBLD family members that drive their molecular activities...
October 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28887161/loss-of-discoidin-domain-receptor-1-ddr1-via-cpg-methylation-during-emt-in-epithelial-ovarian-cancer
#11
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
#12
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
#13
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
#14
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/28765888/edil3-knockdown-inhibits-retinal-angiogenesis-through-the-induction-of-cell-cycle-arrest-in%C3%A2-vitro
#15
Wei Shen, Shanbang Zhu, Haifeng Qin, Ming Zhong, Jinhui Wu, Rui Zhang, Hongyuan Song
Pathological retinal angiogenesis is one of the most common causes of blindness, with limited treatment options being currently available. Epidermal growth factor (EGF)‑like repeat and discoidin I‑like domain‑containing protein 3 (EDIL3) has been reported to serve an important role in embryonic vasculogenesis and tumor angiogenesis; however, its implication in retinal angiogenesis has yet to be elucidated. The present study aimed to investigate the putative roles of EDIL3 in retinal endothelial cells...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28754957/ddr2-controls-the-epithelial-mesenchymal-transition-related-gene-expression-via-c-myb-acetylation-upon-matrix-stiffening
#16
Daehwan Kim, Eunae You, Jangho Jeong, Panseon Ko, Jung-Woong Kim, Sangmyung Rhee
Increasing matrix stiffness caused by the extracellular matrix (ECM) deposition surrounding cancer cells is accompanied by epithelial-mesenchymal transition (EMT). Here, we show that expression levels of EMT marker genes along with discoidin domain receptor 2 (DDR2) can increase upon matrix stiffening. DDR2 silencing by short hairpin RNA downregulated EMT markers. Promoter analysis and chromatin immunoprecipitation revealed that c-Myb and LEF1 may be responsible for DDR2 induction during cell culture on a stiff matrix...
July 28, 2017: Scientific Reports
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
#17
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
#18
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/28700752/role-of-a-novel-immune-modulating-ddr2-expressing-population-in-silica-induced-pulmonary-fibrosis
#19
Lindsay T McDonald, Sara D Johnson, Dayvia L Russell, M Rita I Young, Amanda C LaRue
Micro-injuries associated with chronic inhaled particle exposures are linked with activation of the immune response and are thought to contribute to progression of fibrotic disease. In the pulmonary environment, we have previously demonstrated a heterogeneous population of circulating fibroblast precursors (CFPs), which are defined by expression of the pan-leukocyte marker CD45 and the collagen receptor, discoidin domain receptor-2 (DDR2). This population is derived from the hematopoietic stem cell, expresses collagen, and has a fibroblastic morphology in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28676216/functional-analysis-of-discoidin-domain-receptor-2-mutation-and-expression-in-squamous-cell-lung-cancer
#20
Naomi Kobayashi-Watanabe, Akemi Sato, Tatsuro Watanabe, Tomonori Abe, Chiho Nakashima, Eisaburo Sueoka, Shinya Kimura, Naoko Sueoka-Aragane
OBJECTIVES: Discoidin domain receptor (DDR) 2 mutations have recently been reported to be candidate targets of molecular therapy in lung squamous cell carcinoma (SQCC). However, the status of DDR2 expression and mutations, as well as their precise roles in lung SQCC, have not been clarified. We here report DDR2 mutation and expression status in clinical samples and its role of lung SQCC. MATERIALS AND METHODS: We investigated DDR2 expression and mutation status in 44 human clinical samples and 7 cell lines...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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