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https://www.readbyqxmd.com/read/28241021/extracellular-vesicles-mediate-signaling-between-the-aqueous-humor-producing-and-draining-cells-in-the-ocular-system
#1
Natalie Lerner, Sofia Avissar, Elie Beit-Yannai
PURPOSE: Canonical Wnt signaling is associated with glaucoma pathogenesis and intraocular pressure (IOP) regulation. Our goal was to gain insight into the influence of non-pigmented ciliary epithelium (NPCE)-derived exosomes on Wnt signaling by trabecular meshwork (TM) cells. The potential impact of exosomes on Wnt signaling in the ocular drainage system remains poorly understood. METHODS: Exosomes isolated from media collected from cultured NPCE cells by differential ultracentrifugation were characterized by dynamic light scattering (DLS), tunable resistive pulse sensing (TRPS), and nanoparticle tracking analysis (NTA), sucrose density gradient migration and transmission electron microscopy (TEM)...
2017: PloS One
https://www.readbyqxmd.com/read/28240680/inhibition-of-wnt-signaling-reduces-differentiation-and-induces-sensitivity-to-doxorubicin-in-human-malignant-neuroblastoma-sh-sy5y-cells
#2
Junjira Suebsoonthron, Thiranut Jaroonwitchawan, Montarop Yamabhai, Parinya Noisa
Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme...
February 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28240604/autocrine-lysophosphatidic-acid-signaling-activates-%C3%AE-catenin-and-promotes-lung-allograft-fibrosis
#3
Pengxiu Cao, Yoshiro Aoki, Linda Badri, Natalie M Walker, Casey M Manning, Amir Lagstein, Eric R Fearon, Vibha N Lama
Tissue fibrosis is the primary cause of long-term graft failure after organ transplantation. In lung allografts, progressive terminal airway fibrosis leads to an irreversible decline in lung function termed bronchiolitis obliterans syndrome (BOS). Here, we have identified an autocrine pathway linking nuclear factor of activated T cells 2 (NFAT1), autotaxin (ATX), lysophosphatidic acid (LPA), and β-catenin that contributes to progression of fibrosis in lung allografts. Mesenchymal cells (MCs) derived from fibrotic lung allografts (BOS MCs) demonstrated constitutive nuclear β-catenin expression that was dependent on autocrine ATX secretion and LPA signaling...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28240364/n-cadherin-regulation-of-bone-growth-and-homeostasis-is-osteolineage-stage-specific
#4
Francesca Fontana, Cynthia L Hickman-Brecks, Valerie S Salazar, Leila Revollo, Grazia Abou-Ezzi, Susan K Grimston, Sung Yeop Jeong, Marcus Watkins, Manuela Fortunato, Yael Alippe, Daniel C Link, Gabriel Mbalaviele, Roberto Civitelli
N-cadherin inhibits osteogenic cell differentiation and canonical Wnt/β-catenin signaling in vitro. However, in vivo both conditional Cdh2 ablation and overexpression in osteoblasts lead to low bone mass. We tested the hypothesis that N-cadherin has different effects on osteolineage cells depending upon their differentiation stage. Embryonic conditional osteolineage Cdh2 deletion in mice results in defective growth, low bone mass and reduced osteoprogenitor number. These abnormalities are prevented by delaying Cdh2 ablation until 1 month of age, thus targeting only committed and mature osteoblasts, suggesting they are the consequence of N-cadherin deficiency in osteoprogenitors...
February 27, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28239825/upregulated-serum-sclerostin-level-in-the-t2dm-patients-with-femur-fracture-inhibits-the-expression-of-bone-formation-remodeling-associated-biomarkers-via-antagonizing-wnt-signaling
#5
Y Wu, S-Y Xu, S-Y Liu, L Xu, S-Y Deng, Y-B He, S-C Xian, Y-H Liu, G-X Ni
OBJECTIVE: Bone formation/remodeling-associated biomarkers, such as osteocalcin, amino pro-peptide of type 1 collagen (P1NP) and CrossLaps (CTX) have been deregulated in type 2 diabetes mellitus (T2DM) patients. In particular, the T2DM-associated sclerostin markedly inhibits the bone formation, suppresses the osteoblast activity and downregulates the bone turnover. PATIENTS AND METHODS: In the present study, we examined the serum levels of sclerostin, osteocalcin, P1NP and CTX in the T2DM patients...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28239820/long-non-coding-rna-neat1-acts-as-oncogene-in-nsclc-by-regulating-the-wnt-signaling-pathway
#6
S-J Sun, Q Lin, J-X Ma, W-W Shi, B Yang, F Li
OBJECTIVE: The present study aimed to explore the role of long non-coding RNA NEAT1 (NEAT1) in mediating non-small cell lung cancer (NSCLC) cell migration and invasion, as well as the underlying regulatory mechanisms. PATIENTS AND METHODS: The NEAT1 expression in NSCLC tissues and cell lines was measured using reverse transcription‑quantitative polymerase chain reaction (RT-qPCR). The relationships between NEAT1 expression and clinicopathological parameters were examined by chi-square test...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28238906/fibulin-4-reduces-extracellular-matrix-production-and-suppresses-chondrocyte-differentiation-via-dkk1-mediated-canonical-wnt-%C3%AE-catenin-signaling
#7
Lei Shangguan, Guangzhi Ning, Zhuojing Luo, Yue Zhou
Fibulin-4 is an extracellular matrix (ECM) protein implicated in connective tissue development and elastic fiber formation. However, little is known about the underlying function of Fibulin-4 in cartilage development. The aim of this study was to investigate the role and probable mechanism of Fibulin-4 stimulation in ECM production and chondrocyte differentiation. Fibulin-4 has been observed to be abnormally elevated and matrix metalloproteinases 13 (MMP13) level was highly expressed in human osteoarthritis (OA) chondrocytes...
February 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28238494/important-role-of-collective-cell-migration-and-nerve-fiber-density-in-the-development-of-deep-nodular-endometriosis
#8
Renan Orellana, Javier García-Solares, Jacques Donnez, Olivier van Kerk, Marie-Madeleine Dolmans, Olivier Donnez
OBJECTIVE: To evaluate deep nodular endometriotic lesions induced in baboons over 12 months and analyze collective cell migration and nerve fiber density. DESIGN: Morphologic and immunohistochemical analysis of endometriotic lesions induced in baboons over the course of 1 year. SETTING: Academic research unit. ANIMAL(S): Three female baboons (Papio anubis). INTERVENTION(S): Recovery of induced deep nodular endometriotic nodules from baboons...
February 23, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28237811/the-capz-interacting-protein-rcsd1-is-required-for-cardiogenesis-downstream-of-wnt11a-in-xenopus-laevis
#9
Annemarie Hempel, Susanne J Kühl, Melanie Rothe, Purushothama Rao Tata, Ioan Ovidiu Sirbu, Seppo Vainio, Michael Kühl
Wnt proteins are critical for embryonic cardiogenesis and cardiomyogenesis by regulating different intracellular signalling pathways. Whereas canonical Wnt/β-catenin signalling is required for mesoderm induction and proliferation of cardiac progenitor cells, β-catenin independent, non-canonical Wnt signalling regulates cardiac specification and terminal differentiation. Although the diverse cardiac malformations associated with the loss of non-canonical Wnt11 in mice such as outflow tract (OFT) defects, reduced ventricular trabeculation, myofibrillar disorganization and reduced cardiac marker gene expression are well described, the underlying molecular mechanisms are still not completely understood...
February 22, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28237489/expression-and-clinical-significance-of-high-risk-human-papillomavirus-and-invasive-gene-in-cervical-carcinoma
#10
Zhai Lu, Hua Chen, Xiao-Mei Zheng, Man-Ling Chen
OBJECTIVE: To study the expression of E6 and E7 mRNA in high-risk human papillomavirus (HPV) HPV-18 and the relationship between the expression of invasive gene and cervical carcinoma. METHODS: A total of 119 patients with cervical cancer, cervical erosion and cervical HPV infection who were diagnosed in our hospital were selected and randomly divided into two groups: cervical cancer group (n = 58) and non-cancerous group (n = 61). Another 60 patients with uterine leiomyoma were selected as normal control group...
February 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28237397/sox17-regulates-cholangiocyte-differentiation-and-acts-as-a-tumor-suppressor-in-cholangiocarcinoma
#11
M Merino-Azpitarte, E Lozano, M J Perugorria, A Esparza-Baquer, O Erice, A Santos-Laso, C J O'Rourke, J B Andersen, R Jiménez-Agüero, A Lacasta, M D'Amato, O Briz, N Jalan-Sakrikar, R C Huebert, K M Thelen, S A Gradilone, A M Aransay, J L Lavín, M G Fernández-Barrena, A Matheu, M Marzioni, G J Gores, L Bujanda, J J G Marin, J M Banales
BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a biliary malignancy linked to genetic and epigenetic abnormalities, such as hypermethylation of SOX17 promoter. Here, the role of SOX17 in cholangiocyte differentiation and cholangiocarcinogenesis was studied. METHODS: SOX17 expression/function was evaluated along the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation process of normal human cholangiocytes (NHC) in culture and in cholangiocarcinogenesis...
February 22, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28237244/early-events-in-the-assembly-of-e-cadherin-adhesions
#12
REVIEW
Kabir H Biswas, Ronen Zaidel-Bar
E-cadherin is a calcium dependent cell adhesion molecule that is key to the organization of cells in the epithelial tissue. It is a multidomain, trans-membrane protein in which the extracellular domain forms the homotypic, adhesive interaction while the intracellular domain interacts with the actin cytoskeleton through the catenin family of adaptor proteins. A number of recent studies have provided novel insights into the mechanism of adhesion formation by this class of adhesion proteins. Here, we describe an updated view of the process of E-cadherin adhesion formation with an emphasis on the role of molecular mobility, clustering, and active cellular processes...
February 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28237093/mir-26a-enhances-invasive-capacity-by-suppressing-gsk3%C3%AE-in-human-lung-cancer-cells
#13
Gaoyang Lin, Boning Liu, Zhaowei Meng, Yunde Liu, Xuebing Li, Xiang Wu, Qinghua Zhou, Ke Xu
Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells...
February 21, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28236965/ror-family-receptor-tyrosine-kinases
#14
Sigmar Stricker, Verena Rauschenberger, Alexandra Schambony
ROR-family receptor tyrosine kinases form a small subfamily of receptor tyrosine kinases (RTKs), characterized by a conserved, unique domain architecture. ROR RTKs are evolutionary conserved throughout the animal kingdom and act as alternative receptors and coreceptors of WNT ligands. The intracellular signaling cascades activated downstream of ROR receptors are diverse, including but not limited to ROR-Frizzled-mediated activation of planar cell polarity signaling, RTK-like signaling, and antagonistic regulation of WNT/β-Catenin signaling...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28231524/discovery-of-novel-cdk8-inhibitors-using-multiple-crystal-structures-in-docking-based-virtual-screening
#15
Taijin Wang, Zhuang Yang, Yongguang Zhang, Wei Yan, Fang Wang, Linhong He, Yuanyuan Zhou, Lijuan Chen
The cyclin dependent kinase CDK8, along with Med12 and Med13, form the kinase module of the Mediator complex. CDK8 expression associates with the activation of β-catenin in colon and gastric cancers. Herein, we applied docking-based virtual screening (VS) using the multiple crystal structures to identify several potent CDK8 inhibitors. The appropriate use of multiple crystal structures obtained a better enrichment of CDK8 conformations to cope with the protein flexibility. Later on, the 2D similarity search was used to find the derivatives of the high inhibitory CDK8 inhibitors we discovered by VS...
February 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28231263/uniformity-under-in-vitro-conditions-changes-in-the-phenotype-of-cancer-cell-lines-derived-from-different-medulloblastoma-subgroups
#16
Petr Chlapek, Karel Zitterbart, Leos Kren, Lenka Filipova, Jaroslav Sterba, Renata Veselska
Medulloblastoma comprises four main subgroups (WNT, SHH, Group 3 and Group 4) originally defined by transcriptional profiling. In primary medulloblastoma tissues, these groups are thought to be distinguishable using the immunohistochemical detection of β-catenin, filamin A, GAB1 and YAP1 protein markers. To investigate the utility of these markers for in vitro studies using medulloblastoma cell lines, immunoblotting and indirect immunofluorescence were employed for the detection of β-catenin, filamin A, GAB1 and YAP1 in both DAOY and D283 Med reference cell lines and the panel of six medulloblastoma cell lines derived in our laboratory from the primary tumor tissues of known molecular subgroups...
2017: PloS One
https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#17
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230774/inhibition-of-ccar1-a-coactivator-of-%C3%AE-catenin-suppresses-the-proliferation-and-migration-of-gastric-cancer-cells
#18
Te-Sheng Chang, Kuo-Liang Wei, Chung-Kuang Lu, Yi-Hsing Chen, Ying-Tung Cheng, Shui-Yi Tung, Cheng-Shyong Wu, Ming-Ko Chiang
The aberrant activation of Wnt signaling has been implicated in a variety of human cancers, including gastric cancer. Given the current hypothesis that cancer arises from cancer stem cells (CSCs), targeting the critical signaling pathways that support CSC self-renewal appears to be a useful approach for cancer therapy. Cell cycle and apoptosis regulator 1 (CCAR1) is a transcriptional coactivator which has been shown to be a component of Wnt/β-catenin signaling, and which plays an important role in transcriptional regulation by β-catenin...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230291/therapeutic-potentials-of-bdnf-trkb-in-breast-cancer-current-status-and-perspectives
#19
Amir Tajbakhsh, Amin Mokhtari-Zaer, Mehdi Rezaee, Fahimeh Afzaljavan, Mehdi Rivandi, Seyed Mahdi Hassanian, Gordon A Ferns, Alireza Pasdar, Amir Avan
Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB and the p75(NTR) death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#20
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
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