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https://www.readbyqxmd.com/read/27911269/the-matricellular-protein-cyr61-promotes-breast-cancer-lung-metastasis-by-facilitating-tumor-cell-extravasation-and-suppressing-anoikis
#1
Yu-Ting Huang, Qiang Lan, Girieca Lorusso, Nathalie Duffey, Curzio Rüegg
Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression. Here, we investigated the role of CYR61 in breast cancer lung metastasis using the triple negative human breast cancer cell lines MDA-MB-231 and SUM159...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903483/therapeutic-benefits-and-adverse-effects-of-combined-pro-angiogenic-gene-therapy-in-mouse-critical-leg-ischemia
#2
Benoît Lebas, Julien Galley, Edith Renaud-Gabardos, Françoise Pujol, Françoise Lenfant, Barbara Garmy-Susini, Xavier Chaufour, Anne-Catherine Prats
OBJECTIVE: Critical leg ischemia (CLI) represents the ultimate stage of peripheral arterial disease. Despite current surgery advances, patients with CLI have limited therapeutic options. Therapeutic angiogenesis thus appears as a powerful approach, aiming to stimulate vessel formation by angiogenic molecules administration. In this context, combined gene therapy has proved the most efficient. The present study aims to compare, in a preclinical mouse model, the therapeutic benefit of a combination of two angiogenic factors FGF2 (fibroblast growth factor 2) and Cyr61 using plasmid and viral vectors, able to generate short or long-term transgene expression in the leg, respectively...
November 26, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27889647/activation-of-wnt-%C3%AE-catenin-signaling-enhances-pancreatic-cancer-development-and-the-malignant-potential-via-up-regulation-of-cyr61
#3
Makoto Sano, David R Driscoll, Wilfredo E DeJesus-Monge, Brian Quattrochi, Victoria A Appleman, Jianhong Ou, Lihua Julie Zhu, Nao Yoshida, Shintaro Yamazaki, Tadatoshi Takayama, Masahiko Sugitani, Norimichi Nemoto, David S Klimstra, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras(G12D), Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin(S37A) and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27878658/role-of-matricellular-proteins-in-disorders-of-the-central-nervous-system
#4
A R Jayakumar, A Apeksha, M D Norenberg
Matricellular proteins (MCPs) are actively expressed non-structural proteins present in the extracellular matrix, which rapidly turnover and possess regulatory roles, as well as mediate cell-cell interactions. MCPs characteristically contain binding sites for other extracellular proteins, cell surface receptors, growth factors, cytokines and proteases, that provide structural support for surrounding cells. MCPs are present in most organs, including brain, and play a major role in cell-cell interactions and tissue repair...
November 23, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27863006/the-role-of-ccn5-wisp2-protein-in-pancreatic-islets
#5
REVIEW
Jun-Li Liu, Nancy Kaddour, Subrata Chowdhury, Qing Li, Zu-Hua Gao
In search of direct targets of IGF-I action, we discovered CCN5/WISP2 as a novel protein expressed in pancreatic β-cells. As a member of Cyr61 (connective tissue growth factor in human), CTGF (cysteine rich 61, in mouse), and Nov (nephroblastoma overexpressed, in chicken) family, IGF-I together with Wnt signaling stimulate its expression. When overexpressed in insulinoma cells, CCN5 promotes cell proliferation and cell survival against streptozotocin-induced cell death. The cell proliferation effect seems to be caused by AKT phosphorylation and increased cyclin D1 level...
November 12, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27856305/cyr61-ccn1-is-involved-in-the-pathogenesis-of-psoriasis-vulgaris-via-promoting-il-8-production-by-keratinocytes-in-a-jnk-nf-%C3%AE%C2%BAb-pathway
#6
Pinru Wu, Gang Ma, Xianjin Zhu, Ting Gu, Jie Zhang, Yue Sun, Hui Xu, Rongfen Huo, Beiqing Wang, Baihua Shen, Xiangdong Chen, Ningli Li
PURPOSE: Interleukin-8 (IL-8) is an important factor in the pathogenesis of psoriasis vulgaris, which is characterized by proliferation of keratinocytes, neutrophil infiltration and angiogenesis. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. Whether Cyr61 is involved in the development of psoriasis vulgaris via IL-8 production remains unknown. In this study we explore the role of Cyr61 in IL-8 expression regulation in vivo and in vitro...
November 14, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27829832/members-of-the-cyr61-ctgf-nov-protein-family-emerging-players-in-hepatic-progenitor-cell-activation-and-intrahepatic-cholangiocarcinoma
#7
Qunfeng Wu, Marda Jorgensen, Joanna Song, Junmei Zhou, Chen Liu, Liya Pi
Hepatic stem/progenitor cells (HPC) reside quiescently in normal biliary trees and are activated in the form of ductular reactions during severe liver damage when the replicative ability of hepatocytes is inhibited. HPC niches are full of profibrotic stimuli favoring scarring and hepatocarcinogenesis. The Cyr61/CTGF/NOV (CCN) protein family consists of six members, CCN1/CYR61, CCN2/CTGF, CCN3/NOV, CCN4/WISP1, CCN5/WISP2, and CCN6/WISP3, which function as extracellular signaling modulators to mediate cell-matrix interaction during angiogenesis, wound healing, fibrosis, and tumorigenesis...
2016: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/27819674/mmtv-cre-ccn6-knockout-mice-develop-tumors-recapitulating-human-metaplastic-breast-carcinomas
#8
E E Martin, W Huang, T Anwar, C Arellano-Garcia, B Burman, J-L Guan, M E Gonzalez, C G Kleer
Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly downregulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27760754/lysophosphatidic-acid-induced-vascular-neointimal-formation-in-mouse-carotid-arteries-is-mediated-by-the-matricellular-protein-ccn1-cyr61
#9
Feng Hao, Fuqiang Zhang, Daniel Dongwei Wu, Dong An, Jing Shi, Guohong Li, Xuemin Xu, Mei-Zhen Cui
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation...
October 19, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27759760/validity-of-klotho-cyr61-and-ykl-40-as-ideal-predictive-biomarkers-for-acute-kidney-injury-review-study
#10
Osama Mosa, Milan Skitek, Ales Jerin
CONTEXT AND OBJECTIVE: Acute kidney injury (AKI) is still a headache for clinicians and scientists as a possible reason for increased death among intensive care unit (ICU) patients after invasive cardiac surgery. Furthermore, the diagnostic process for AKI using conventional biomarkers is not sufficient to ensure early warning of this condition because of the morbid influence of non-renal factors that definitively delay the time for the prognosis. These imposed limitations have led to significant amounts of research targeted towards identifying novel biomarkers for AKI with a sustained degree of sensitivity and specificity...
October 13, 2016: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/27743169/serum-cyr61-as-a-potential-biomarker-for-diagnosis-of-colorectal-cancer
#11
Y F Song, Z B Xu, X J Zhu, X Tao, J L Liu, F L Gao, C L Wu, B Song, Q Lin
PURPOSE: To determine the sensitivity and specificity of serum Cyr61 as a potential biomarker for the diagnosis of colorectal cancer (CRC) and to assess the association between serum Cyr61 level and CRC clinicopathological status. METHODS: We used an enzyme-linked immunosorbent assay to measure serum Cyr61 in patients with CRC, patients with colorectal adenomas, and healthy controls. We also analyzed the relationship between serum Cyr61 and clinicopathological features of CRC patients...
October 14, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27734404/an-analysis-of-pathological-activities-of-ccn-proteins-in-joint-disorders-mechanical-stretch-mediated-ccn2-expression-in-cultured-meniscus-cells
#12
Takayuki Furumatsu, Toshifumi Ozaki
The multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, also known as connective tissue growth factor, regulates cellular proliferation, differentiation, and tissue regeneration. Recent literatures have described important roles of CCN2 in the meniscus metabolism. However, the mechanical stress-mediated transcriptional regulation of CCN2 in the meniscus remains unclear. The meniscus is a fibrocartilaginous tissue that controls complex biomechanics of the knee joint. Therefore, the injured unstable meniscus has a poor healing potential especially in the avascular inner region...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734389/construction-and-analysis-of-an-allelic-series-of-ccn1-knockin-mice
#13
Ricardo I Monzon, Ki-Hyun Kim, Lester F Lau
The embryonic lethality of mice with conventional global knockout of Ccn1 (Cyr61) precludes analysis of Ccn1 functions in late embryonic development or in adulthood. To circumvent this limitation, we have generated conditional knockout mice that allow cell type-specific deletion of Ccn1, and constructed an allelic series of Ccn1 knockin mice that express CCN1 defective for binding specific integrins in lieu of the wild type protein. Here we describe the construction of these mice and discuss how analysis of these animals can provide unique insights into Ccn1 functions mediated through specific integrin receptors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27733378/function-and-hormonal-regulation-of-gata3-in-human-first-trimester-placentation
#14
Bora Lee, Lindsay L Kroener, Ning Xu, Erica T Wang, Alexandra Banks, John Williams, Mark O Goodarzi, Yii-der I Chen, Jie Tang, Yizhou Wang, Vineela Gangalapudi, Margareta D Pisarska
Pregnancies resulting from fresh in-vitro fertilization (IVF) cycles exposed to supra-physiologic estrogen levels have been associated with higher rates of low birth weight and small for gestational age babies. We identified GATA3, a transcription factor selectively expressed in the trophectoderm during the blastocyst stage of embryo development, in an upstream analysis of genes that were differentially methylated in chorionic villus samples between IVF and non-IVF infertility treatment (NIFT) pregnancies. In this study, we investigate the hypothesis that GATA3 is hormonally regulated and plays an important functional role in trophoblast migration, invasion and placentation...
October 12, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27725691/cyr61-participates-in-the-pathogenesis-of-acute-lymphoblastic-leukemia-by-enhancing-cellular-survival-via-the-akt-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Xianjin Zhu, Yanfang Song, Conglian Wu, Chuxi Pan, Pingxia Lu, Meihua Wang, Peizheng Zheng, Rongfen Huo, Chenqing Zhang, Wanting Li, Yulin Lin, Yingping Cao, Ningli Li
Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients...
October 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721245/positive-correlation-of-cysteine-rich-61-and-target-genes-of-wnt-%C3%AE-catenin-pathway-in-esophageal-squamous-cell-carcinoma
#16
Peng Wang, Li Li, Ting Li
OBJECTIVES: To analyze the relationship between cysteine-rich 61 (Cyr61) and target genes of Wnt/β-catenin pathway (CCND1 and MYC) in 40 esophageal squamous cell carcinoma (ESCC) tissue specimens. Another aim of this study was to verify whether Cyr61 could be regulated by Wnt/β-catenin signaling. MATERIALS AND METHODS: Forty ESCC tissue specimens with paired adjacent normal epithelial tissues were obtained. The expression of Cyr61, CCND1, and MYC was examined by quantitative real-time polymerase chain reaction...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/27713913/the-metastasis-inducer-ccn1-cyr61-activates-the-fatty-acid-synthase-fasn-driven-lipogenic-phenotype-in-breast-cancer-cells
#17
Javier A Menendez, Luciano Vellon, Ingrid Espinoza, Ruth Lupu
The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation...
2016: Oncoscience
https://www.readbyqxmd.com/read/27705906/cyr61-positive-cancer-stem-like-cells-enhances-distal-metastases-of-pancreatic-cancer
#18
Weidong Shi, Chenyue Zhang, Zhen Chen, Hao Chen, Luming Liu, Zhiqiang Meng
Efficient inhibition of tumor metastasis after resection of primary tumors is critical for cancer therapy. We have recently shown that Cyr61 promotes growth of pancreatic ductal adenocarcinoma (PDAC) through PI3k/Akt signaling-enhanced nuclear exclusion of p27. Here, we report that administration of adeno-associated viral vectors carrying a short-hairpin interfering RNA (shRNA) for Cyr61 via pancreatic duct significantly decreased the distal tumor metastases after resection of primary pancreatic tumor in mice...
September 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27696408/widespread-brain-transcriptome-alterations-underlie-the-neuroprotective-actions-of-dietary-saffron
#19
Nicholas V Skladnev, Varshika Ganeshan, Ji Yeon Kim, Thomas J Burton, John Mitrofanis, Jonathan Stone, Daniel M Johnstone
Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for 2, 5 or 10 days before administration of the parkinsonian neurotoxin MPTP (50 mg/kg)...
October 1, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27671657/flow-dependent-yap-taz-activities-regulate-endothelial-phenotypes-and-atherosclerosis
#20
Kuei-Chun Wang, Yi-Ting Yeh, Phu Nguyen, Elaine Limqueco, Jocelyn Lopez, Satenick Thorossian, Kun-Liang Guan, Yi-Shuan J Li, Shu Chien
The focal nature of atherosclerotic lesions suggests an important role of local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechanotransduction and vascular homeostasis. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of atheroprone endothelial phenotypes and the consequential development of atherosclerotic lesions. We found that exposure of cultured endothelial cells (ECs) to the atheroprone disturbed flow resulted in YAP/TAZ activation and translocation into EC nucleus to up-regulate the target genes, including cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
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