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https://www.readbyqxmd.com/read/29213214/ror2-receptor-promotes-the-migration-of-osteosarcoma-cells-in-response-to-wnt5a
#1
Bin Dai, Ting Yan, Ailiang Zhang
Background: We have reported that the phosphatidylinositol-3 kinase (PI3K)/Akt/RhoA signaling pathway mediates Wnt5a-induced cell migration of osteosarcoma cells. However, the specific receptors responding to Wnt5a ligand remain poorly defined in osteosarcoma metastasis. Methods: Wound healing assays were used to measure the migration rate of osteosarcoma cells transfected with shRNA or siRNA specific against ROR2 or indicated constructs. We evaluated the RhoA activation in osteosarcoma MG-63 and U2OS cells with RhoA activation assay...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29162033/identification-of-genome-wide-snp-snp-interactions-associated-with-important-traits-in-chicken
#2
Hui Zhang, Jia-Qiang Yu, Li-Li Yang, Luke M Kramer, Xin-Yang Zhang, Wei Na, James M Reecy, Hui Li
BACKGROUND: In addition to additive genetic effects, epistatic interactions can play key roles in the control of phenotypic variation of traits of interest. In the current study, 475 male birds from lean and fat chicken lines were utilized as a resource population to detect significant epistatic effects associated with growth and carcass traits. RESULTS: A total of 421 significant epistatic effects were associated with testis weight (TeW), from which 11 sub-networks (Sub-network1 to Sub-network11) were constructed...
November 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29151594/adipocytes-sustain-pancreatic-cancer-progression-through-a-non-canonical-wnt-paracrine-network-inducing-ror2-nuclear-shuttling
#3
C Carbone, G Piro, N Gaianigo, F Ligorio, R Santoro, V Merz, F Simionato, C Zecchetto, G Falco, G Conti, P T Kamga, M Krampera, F Di Nicolantonio, L De Franceschi, A Scarpa, G Tortora, D Melisi
BACKGROUND: Solid epidemiological evidences connect obesity with incidence, stage, and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions. METHODS: We studied the role of factors secreted by two adipogenic model systems from primary human Bone Marrow Stromal Cells (hBMSC) in an in vitro experimental cell transformation model system of human pancreatic ductal epithelial (HPDE) cell stably expressing activated KRAS (HPDE/KRAS),RESULTS:We measured a significant induction of EMT and aggressiveness in HPDE and HPDE/KRAS cell lines when cultured with medium conditioned by fully differentiated adipocytes (ADIPO(CM)) if compared with the same cells cultured with medium conditioned by hBMSC (hBMSC(CM)) from two different healthy donors...
November 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29113233/higher-expression-level-of-tyrosine-kinase-like-orphan-receptor-2-and-wnt-member-5a-in-papillary-thyroid-carcinoma-is-associated-with-poor-prognosis
#4
Liang Chen, Lianmei Zhao, Mingjian Ding, Meng Yang, Wenhua Yang, Guozhong Cui, Baoen Shan
The tyrosine kinase-like orphan receptor 2 (ROR2) has a wnt-mediated, pro-tumorigenic role in certain types of cancer. The present study was designed to assess the protein expression level of ROR2 and its putative ligand Wnt member 5a (Wnt5a), as well as the association with clinicopathological features in papillary thyroid carcinoma (PTC). A total of 58 patients were recruited, resulting in 58 human PTC tissue samples and their paired adjacent noncancerous tissue samples being obtained. The protein expression levels of ROR2 and Wnt5a were evaluated by immunohistochemistry and western blotting, and messenger RNA expression levels were determined by reverse transcription-quantitative polymerase chain reaction...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29070775/expression-of-ror2-associated-with-fibrosis-of-the-submandibular-gland
#5
Daiki Takahashi, Hiroaki Suzuki, Yasumasa Kakei, Kimi Yamakoshi, Yasuhiro Minami, Takahide Komori, Michiru Nishita
The submandibular gland (SMG) is one of the major salivary glands that play important roles for variety of physiological functions, such as digestion of foods, prevention of infection, and lubrication of the mouth. Dysfunction of the SMG, often associated with a salivary inflammation, adversely influences a person's quality of life. However, the mechanism underlying inflammation-driven dysfunction of the SMG is largely unknown. Here, we used a mouse model in which the main excretory duct of the SMG is ligated unilaterally to induce inflammation of the gland and examined the expression of Wnt5a, Ror1 and Ror2 genes, encoding Wnt5a ligand and its cognate receptors, which have been implicated in tissue damage or inflammatory responses in variety of tissues...
October 25, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/29058491/a-review-of-primary-thyroid-lymphoma-molecular-factors-diagnosis-and-management
#6
Efstathios T Pavlidis, Theodoros E Pavlidis
Purpose/aim: To focus on current aspects of primary thyroid lymphoma (PTL), which is a rare clinical entity usually manifested by a rapidly growing mass in the neck that can cause pressure symptoms. MATERIALS AND METHODS: Relevant papers in PubMed published through June 2017 were selected to track updated information about PTL with an emphasis on diagnosis and novel therapeutic management. RESULTS: The most frequent cases include non-Hodgkin lymphoma derived from B-cells, mainly diffuse large B-cell lymphoma (DLBCL) followed by mucosa-associated lymphoid tissue (MALT) lymphoma or a mixed type...
October 23, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/29054966/wnt5a-promotes-epithelial-to-mesenchymal-transition-and-metastasis-in-non-small-cell-lung-cancer
#7
Biao Wang, Zhen Tang, Huiyuan Gong, Li Zhu, Xuegang Liu
A recent study indicated that high Wnt5a expression is associated with poor prognosis in NSCLC patients, however, the underlying mechanism was not clear yet. Immunohistochemistry and Western blotting was performed to examine the protein expression level in NSCLC tissues and cell lines. The role of Wnt5a in clone formation, invasiveness, migration and epithelial-to-mesenchymal transition (EMT) of NSCLC cells were studied. Luciferase reporter assay was used to evaluate the Tcf/Lef transcriptional activity. For assessing the effects of Wnt5a on tumor growth and metastasis in vivo , A549 cells transfected with sh-Wnt5a were subcutaneously or orthotopically injected into nude mice...
October 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28979270/functional-characterization-of-a-syntaxin-involved-in-tomato-solanum-lycopersicum-resistance-against-powdery-mildew
#8
Valentina Bracuto, Michela Appiano, Zheng Zheng, Anne-Marie A Wolters, Zhe Yan, Luigi Ricciardi, Richard G F Visser, Stefano Pavan, Yuling Bai
Specific syntaxins, such as Arabidopsis AtPEN1 and its barley ortholog ROR2, play a major role in plant defense against powdery mildews. Indeed, the impairment of these genes results in increased fungal penetration in both host and non-host interactions. In this study, a genome-wide survey allowed the identification of 21 tomato syntaxins. Two of them, named SlPEN1a and SlPEN1b, are closely related to AtPEN1. RNAi-based silencing of SlPEN1a in a tomato line carrying a loss-of-function mutation of the susceptibility gene SlMLO1 led to compromised resistance toward the tomato powdery mildew fungus Oidium neolycopersici...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28978484/a-wnt-calcium-signaling-cascade-regulates-neuronal-excitability-and-trafficking-of-nmdars
#9
Andrea McQuate, Elena Latorre-Esteves, Andres Barria
Wnt signaling controls multiple biological process, particularly the embryonic development of metazoans. Sustained expression of Wnt signaling components in the mature mammalian CNS and their apparent deregulation in certain neuropathologies suggest that it also plays a part beyond embryonic development to regulate normal brain function. We describe a noncanonical Wnt/Ca(2+) signaling cascade that regulates the electrophysiological intrinsic properties of rat neurons, resulting in sustained membrane depolarization and the mobilization of Ca(2+) from internal stores...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28851822/protein-kinase-n3-promotes-bone-resorption-by-osteoclasts-in-response-to-wnt5a-ror2-signaling
#10
Shunsuke Uehara, Nobuyuki Udagawa, Hideyuki Mukai, Akihiro Ishihara, Kazuhiro Maeda, Teruhito Yamashita, Kohei Murakami, Michiru Nishita, Takashi Nakamura, Shigeaki Kato, Yasuhiro Minami, Naoyuki Takahashi, Yasuhiro Kobayashi
Cytoskeletal reorganization in osteoclasts to form actin rings is necessary for these cells to attach to bone and resorb bone matrices. We delineated the pathway through which Wnt5a signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2) promoted the bone-resorbing activity of osteoclasts. Wnt5a binding to Ror2 stimulated Rho, a small GTPase involved in cytoskeletal reorganization. Subsequently, the Rho effector kinase Pkn3 bound to and enhanced the activity of c-Src, a nonreceptor tyrosine kinase that is critical for actin ring formation...
August 29, 2017: Science Signaling
https://www.readbyqxmd.com/read/28838952/cd55-regulates-self-renewal-and-cisplatin-resistance-in-endometrioid-tumors
#11
Caner Saygin, Andrew Wiechert, Vinay S Rao, Ravi Alluri, Elizabeth Connor, Praveena S Thiagarajan, James S Hale, Yan Li, Anastasia Chumakova, Awad Jarrar, Yvonne Parker, Daniel J Lindner, Anil Belur Nagaraj, J Julie Kim, Analisa DiFeo, Fadi W Abdul-Karim, Chad Michener, Peter G Rose, Robert DeBernardo, Haider Mahdi, Keith R McCrae, Feng Lin, Justin D Lathia, Ofer Reizes
Effective targeting of cancer stem cells (CSCs) requires neutralization of self-renewal and chemoresistance, but these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both of these phenotypes via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs and non-CSCs in endometrioid cancer models. In this context, CD55 functions in a complement-independent manner and required lipid raft localization for CSC maintenance and cisplatin resistance...
September 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28833807/the-wnt5a-receptor-receptor-tyrosine-kinase-like-orphan-receptor-2-is-a-predictive-cell-surface-marker-of-human-mesenchymal-stem-cells-with-an-enhanced-capacity-for-chondrogenic-differentiation
#12
Sally C Dickinson, Catherine A Sutton, Kyla Brady, Anna Salerno, Theoni Katopodi, Rhys L Williams, Christopher C West, Denis Evseenko, Ling Wu, Suzanna Pang, Roberta Ferro de Godoy, Allen E Goodship, Bruno Péault, Ashley W Blom, Wael Kafienah, Anthony P Hollander
Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now, their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here, we identify receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis...
November 2017: Stem Cells
https://www.readbyqxmd.com/read/28818634/mining-na%C3%A3-ve-rabbit-antibody-repertoires-by-phage-display-for-monoclonal-antibodies-of-therapeutic-utility
#13
Haiyong Peng, Thomas Nerreter, Jing Chang, Junpeng Qi, Xiuling Li, Pabalu Karunadharma, Gustavo J Martinez, Mohammad Fallahi, Jo Soden, Jim Freeth, Roger R Beerli, Ulf Grawunder, Michael Hudecek, Christoph Rader
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity...
September 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28790171/the-ror1-receptor-tyrosine-kinase-plays-a-critical-role-in-regulating-satellite-cell-proliferation-during-regeneration-of-injured-muscle
#14
Koki Kamizaki, Ryosuke Doi, Makoto Hayashi, Takeshi Saji, Motoi Kanagawa, Tatsushi Toda, So-Ichiro Fukada, Hsin-Yi Henry Ho, Michael Eldon Greenberg, Mitsuharu Endo, Yasuhiro Minami
The Ror family receptor tyrosine kinases, Ror1 and Ror2, play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remain largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#15
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28681925/wnt5a-suppresses-osteoblastic-differentiation-of-human-periodontal-ligament-stem-cell-like-cells-via-ror2-jnk-signaling
#16
Daigaku Hasegawa, Naohisa Wada, Shinichiro Yoshida, Hiromi Mitarai, Mai Arima, Atsushi Tomokiyo, Sayuri Hamano, Hideki Sugii, Hidefumi Maeda
Wnt5a, a non-canonical Wnt protein, is known to play important roles in several cell functions. However, little is known about the effects of Wnt5a on osteoblastic differentiation of periodontal ligament (PDL) cells. Here, we examined the effects of Wnt5a on osteoblastic differentiation and associated intracellular signaling in human PDL stem/progenitor cells (HPDLSCs). We found that Wnt5a suppressed expression of bone-related genes (ALP, BSP, and Osterix) and alizarin red-positive mineralized nodule formation in HPDLSCs under osteogenic conditions...
July 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28674110/a-cytokine-like-protein-dickkopf-related-protein-3-is-atheroprotective
#17
Baoqi Yu, Stefan Kiechl, Dan Qi, Xiaocong Wang, Yanting Song, Siegfried Weger, Agnes Mayr, Alexandra Le Bras, Eirini Karamariti, Zhongyi Zhang, Ivan Del Barco Barrantes, Christof Niehrs, Georg Schett, Yanhua Hu, Wen Wang, Johann Willeit, Aijuan Qu, Qingbo Xu
BACKGROUND: Dickkopf-related protein 3 (DKK3) is a secreted protein that is involved in the regulation of cardiac remodeling and vascular smooth muscle cell differentiation, but little is known about its role in atherosclerosis. METHODS: We tested the hypothesis that DKK3 is atheroprotective using both epidemiological and experimental approaches. Blood DKK3 levels were measured in the Bruneck Study in 2000 (n=684) and then in 2005 (n=574). DKK3-deficient mice were crossed with apolipoprotein E(-/-) mice to evaluate atherosclerosis development and vessel injury-induced neointimal formation...
September 12, 2017: Circulation
https://www.readbyqxmd.com/read/28662348/abnormal-wnt5a-signaling-causes-mandibular-hypoplasia-in-robinow-syndrome
#18
S Hosseini-Farahabadi, S J Gignac, A Danescu, K Fu, J M Richman
The study of rare genetic diseases provides valuable insights into human gene function. Here, we investigate dominant Robinow syndrome (RS), which affects the WNT5A signaling pathway. Autosomal dominant RS is caused by missense mutations in WNT5A or nonsense mutations in the adaptor protein DVL1 or DVL3. The recessive form of the disease is caused by loss-of-function mutations in the receptor ROR2. RS is characterized by hypertelorism, midface, and mandibular hypoplasia. Here, we focus on the missense mutations in WNT5A, since the impact on function is difficult to predict from in silico analysis...
October 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#19
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
October 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28618961/microrna-208b-inhibits-human-osteosarcoma-progression-by-targeting-ror2
#20
Zhe Jiang, Chunshan Jiang, Chonglong Yu, Jinnv Fang
MicroRNAs are widely involved in cancer progression by inhibiting the expression levels of oncogenes or tumor suppressor genes, and dysregulation of microRNAs may contribute to tumorigenesis. Here, we found that overexpressed miR-208b can reduce the proliferation of human osteosarcoma cell lines U-2OS and Saos-2 by arresting cell cycle progression. The in vivo xenograft tumors induced by Saos-2 cells overexpressing miR-208b had smaller size and grew more slowly than those induced by the control cells. The mobility of U-2OS or Saos-2 cells was also downregulated by miR-208b...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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