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https://www.readbyqxmd.com/read/28650464/%C3%AE-catenin-downregulates-dicer-to-promote-ovarian-cancer-metastasis
#1
S K Y To, A S C Mak, Y M Eva Fung, C-M Che, S-S Li, W Deng, B Ru, J Zhang, A S T Wong
Ovarian cancer is a nearly uniform lethal disease and its highly aggressive metastatic phenotype portends a poor prognosis. Lack of a well-controlled, relevant experimental model has been a major obstacle to identifying key molecules causing metastasis. Here we describe the creation of a new isogenic model of spontaneous human ovarian cancer metastasis exhibiting opposite phenotypes-highly metastatic (HM) and non-metastatic (NM)-both in vitro and in vivo. HM was unique in its ability to metastasize consistently to the peritoneum, mimicking the major dissemination route of human ovarian cancer...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28646562/argininosuccinate-synthase-1-ass1-a-marker-of-unclassified-hepatocellular-adenoma-and-high-bleeding-risk
#2
Elodie Henriet, Aya Abou Hammoud, Jean-William Dupuy, Benjamin Dartigues, Zakaria Ezzoukry, Nathalie Dugot-Senant, Thierry Leste-Lasserre, Nestor Pallares-Lupon, Macha Nikolski, Brigitte Le Bail, Jean-Frédéric Blanc, Charles Balabaud, Paulette Bioulac-Sage, Anne-Aurélie Raymond, Frédéric Saltel
Hepatocellular adenomas (HCA) are rare benign tumors divided into three main subgroups defined by patho-molecular features, HNF1A (H-HCA), mutated β-catenin (b-HCA) and inflammatory (IHCA). In the case of unclassified HCA (UHCA), which are currently identified by default, a high risk of bleeding remains a clinical issue. The objective of this study was to explore UHCA proteome with the aim to identify specific biomarkers. Following dissection of the tumoral (T) and non-tumoral (NT) tissue on formalin-fixed paraffin-embedded (FFPE) from HCA tissue sections using laser capture methodology, we performed mass spectrometry analysis to compare T and NT protein expression levels in HCA, H-HCA, IHCA, b-HCA, UHCA and focal nodular hyperplasia...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28639895/upregulation-of-mir-199a-b-contributes-to-cisplatin-resistance-via-wnt-%C3%AE-catenin-abcg2-signaling-pathway-in-aldha1-colorectal-cancer-stem-cells
#3
Binghe Chen, Dezhong Zhang, Jun Kuai, Mingkun Cheng, Xiangjie Fang, Guangyan Li
Cisplatin resistance in colorectal cancer largely results from the colorectal cancer stem cells which could be targeted to improve the efficacy of chemotherapy. MicroRNAs are possible modulators of cancer stem cell characteristics and maybe involved in the retention of cancer stem cell chemoresistance. The aim of this study was to investigate the biological function of miR-199a/b on cisplatin resistance in colorectal cancer stem cells and its related mechanisms. Here, ALDHA1(+) cells from primary colorectal cancer tissues behaved similar to cancer stem cells and were chemoresistant to cisplatin...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639893/apobec-1-complementation-factor-regulates-cell-migration-and-apoptosis-through-dickkopf1-by-acting-on-its-3-untranslated-region-in-mcf7-cells
#4
Xin Yan, Qianyin Li, Dongsheng Ni, Yajun Xie, Qingling He, Qianya Wan, Yamin Liu, Zhongshi Lyu, Zhaomin Mao, Qin Zhou
A1CF (apobec-1 complementation factor) acts as a component of the apolipoprotein-B messenger RNA editing complex. Previous researches mainly focused on its post-transcriptional cytidine to uridine RNA editing. However, few study reported its role in progression of breast carcinoma cells. Wound healing assay and flow cytometry were applied to detect the migration and apoptosis; western blot, real-time polymerase chain reaction, and dual-luciferase assays were applied to investigate the potential regulation mechanism of A1CF-mediated cell migration and apoptosis...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28637905/p120-catenin-downregulation-and-pik3ca-mutations-cooperate-to-induce-invasion-through-mmp1-in-hnscc
#5
Michal Kidacki, Heather L Lehman, Michelle V Green, Joshua I Warrick, Douglas B Stairs
Despite recent improvements in treatment for Head and Neck Squamous Cell Carcinoma (HNSCC), half of all patients with a regional or advanced disease will die within five years from diagnosis. Therefore, identification of mechanisms driving the aggressive behavior of HNSCC is of utmost importance. Since p120-catenin (CTNND1/P120CTN) downregulation and PIK3CA mutations are commonly found in HNSCC, the objective of this study was to identify their impact on fundamental processes of metastasis, specifically, migration and invasion...
June 21, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28625128/the-wnt-%C3%AE-catenin-signalling-pathway-inhibitor-sclerostin-is-a-biomarker-for-early-atherosclerosis-in-obesity
#6
Djordje S Popovic, Milena Mitrovic, Dragana Tomic-Naglic, Tijana Icin, Ivana Bajkin, Bojan Vukovic, Damir Benc, Zeljko Zivanovic, Branka Kovacev-Zavisic, Edita Stokic
BACKGROUND: Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/β-catenin signalling pathway (WβcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WβcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results...
June 18, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28624869/incorporation-of-cerium-oxide-into-hydroxyapatite-coating-protects-bone-marrow-stromal-cells-against-h2o2-induced-inhibition-of-osteogenic-differentiation
#7
Kai Li, Qingyi Shen, Youtao Xie, Mingyu You, Liping Huang, Xuebin Zheng
Oxidative stress exerts a key influence in osteoporosis in part by inhibiting osteogenic differentiation of bone marrow stromal cells (BMSCs). With their unique antioxidant properties and reported biocompatibility, cerium oxide (CeO2) ceramics exhibit promising potential for the treatment of osteoporosis resulting from oxidative stress. In this study, protective effects of CeO2-incorporated hydroxyapatite coatings (HA-10Ce and HA-30Ce) on the viability and osteogenic differentiation of H2O2-treated BMSCs were examined...
June 17, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28623072/commentary-on-integrative-clinical-genomics-of-advanced-prostate-cancer-robinson-d-van-allen-em-wu-ym-schultz-n-lonigro-rj-mosquera-jm-montgomery-b-taplin-me-pritchard-cc-attard-g-beltran-h-abida-w-bradley-rk-vinson-j-cao-x-vats-p-kunju-lp-hussain-m-feng-fy
#8
Stephen J Freedland, William J Aronson
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28621328/live-cell-screening-platform-identifies-ppar%C3%AE-as-a-regulator-of-cardiomyocyte-proliferation-and-cardiac-repair
#9
Ajit Magadum, Yishu Ding, Lan He, Teayoun Kim, Mohankrishna Dalvoy Vasudevarao, Qinqiang Long, Kevin Yang, Nadeera Wickramasinghe, Harsha V Renikunta, Nicole Dubois, Gilbert Weidinger, Qinglin Yang, Felix B Engel
Zebrafish can efficiently regenerate their heart through cardiomyocyte proliferation. In contrast, mammalian cardiomyocytes stop proliferating shortly after birth, limiting the regenerative capacity of the postnatal mammalian heart. Therefore, if the endogenous potential of postnatal cardiomyocyte proliferation could be enhanced, it could offer a promising future therapy for heart failure patients. Here, we set out to systematically identify small molecules triggering postnatal cardiomyocyte proliferation. By screening chemical compound libraries utilizing a Fucci-based system for assessing cell cycle stages, we identified carbacyclin as an inducer of postnatal cardiomyocyte proliferation...
June 16, 2017: Cell Research
https://www.readbyqxmd.com/read/28621236/dynamic-soluble-changes-in-svegfr1-hgf-and-vegf-promote-chemotherapy-and-bevacizumab-resistance-a-prospective-translational-study-in-the-becox-gemcad-09-01-trial
#10
Estela Pineda, A Salud, E Vila-Navarro, M J Safont, Beatriz Llorente, J Aparicio, R Vera, P Escudero, E Casado, C Bosch, U Bohn, R Pérez-Carrión, A Carmona, J R Ayuso, T Ripollés, R Bouzas, M Gironella, X García-Albéniz, J Feliu, J Maurel
Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28618047/focal-b-catenin-mutation-identified-on-formalin-fixed-and-paraffin-embedded-inflammatory-hepatocellular-adenomas
#11
Joan Saldarriaga, Bettina Bisig, Gabrielle Couchy, Claire Castain, Jessica Zucman-Rossi, Charles Balabaud, Christine Sempoux, Paulette Bioulac-Sage
The identification of hepatocellular adenoma (HCA) with mutation in exon 3 of the CTNNB1 gene encoding for b-catenin is clinically relevant due to higher risk of malignant transformation. Inflammatory HCA (IHCA) can exhibit b-catenin activation (b-IHCA). We report 2 cases with multiple IHCA in which focal b-catenin activation has been found in one of the IHCA. In both cases, the diagnosis of IHCA was confirmed on the resected nodules by routine stains, immunohistochemical detection of C-reactive protein (CRP), and molecular biology on frozen material...
June 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28611108/wnt-%C3%AE-catenin-signaling-contributes-to-tumor-malignancy-and-is-targetable-in-gastrointestinal-stromal-tumor
#12
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Michael J Cavnar, Teresa S Kim, Vinod P Balachandran, Juan A Santamaria-Barria, Noah A Cohen, Michael J Beckman, Benjamin Medina, Ferdinand Rossi, Megan H Crawley, Jennifer K Loo, Joanna H Maltbaek, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. While the Wnt/b-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed b-catenin and contained active, dephosphorylated nuclear b-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28600813/elucidation-of-altered-pathways-in-tumor-initiating-cells-of-triple-negative-breast-cancer-a-useful-cell-model-system-for-drug-screening
#13
Anne G Christensen, Sidse Ehmsen, Mikkel G Terp, Richa Batra, Nicolas Alcaraz, Jan Baumbach, Julie B Noer, José Moreira, Rikke Leth-Larsen, Martin R Larsen, Henrik J Ditzel
A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28600477/targeting-the-wnt-pathway-and-cancer-stem-cells-with-anti-progastrin-humanized-antibodies-a-major-breakthrough-for-k-ras-mutated-colorectal-cancer-treatment
#14
Alexandre Prieur, Monica Cappellini, Guillaume Habif, Marie-Paule Lefranc, Thibault Mazard, Eric Morency, Jean-Marc Pascussi, Maud Flaceliere, Nathalie Cahuzac, Berengere Vire, Benjamin Dubuc, Amandine Durochat, Pierre Liaud, Jérémy Ollier, Caroline Pfeiffer, Sophie Poupeau, Véronique Saywell, Chris Planque, Eric Assenat, Frédéric Bibeau, Jean-François Bourgaux, Pascal Pujol, Alain Sézeur, Marc Ychou, Dominique Joubert
<p>Patients with metastatic colorectal cancer (CRC) suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for the self-renewal of colon CSCs, which is also a direct b-catenin/Tcf4 target gene. In this study we aimed to develop a novel targeted therapy to neutralize secreted progastrin in order to inhibit Wnt signaling, CSCs and reduce relapses.</p> Experimental Design: <p>Antibodies (monoclonal and humanized) directed against progastrin were produced and selected for target specificity and affinity...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28592538/identification-of-il-27-il-27ra-as-a-critical-immune-axis-for-in-vivo-hiv-control
#15
M Ruiz-Riol, D Berdnik, A Llano, B Mothe, C Gálvez, S Pérez-Álvarez, B Oriol-Tordera, A Olvera, S Silva-Arrieta, Michael Meulbroek, Ferran Pujol, J Coll, J Martinez-Picado, C Ganoza, J Sanchez, G Gómez, T Wyss-Coray, C Brander
Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray able to measure >600 plasma proteins involved in cell-to-cell communication was used to measure plasma protein profiles in 96 HIV-infected, treatment-naïve individuals with high (>50,000) or low (<10,000 HIV RNA copies/ml) viral loads...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28586031/punicalagin-suppresses-the-proliferation-and-invasion-of-cervical-cancer-cells-through-inhibition-of-the-%C3%AE-catenin-pathway
#16
Jianming Tang, Bingshu Li, Shasha Hong, Cheng Liu, Jie Min, Ming Hu, Yang Li, Yaodan Liu, Li Hong
Natural botanical drugs have attracted attention due to their cancer chemopreventive and chemotherapeutic properties in cancer. Punicalagin (PUN) is the major bioactive component of pomegranate peel, and has been shown to have antioxidant, anti-inflammatory, antiviral, antiproliferation and anticancer properties. PUN has been shown to induce apoptosis in several cancer cell lines. The aim of the present study was to investigate the effect of PUN on HeLa human cervical cancer cells in vitro. The viability of the HeLa cells was assessed following treatment with PUN (0, 12...
June 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28578904/role-of-ras-wnt-%C3%AE-catenin-axis-activation-in-the-pathogenesis-of-podocyte-injury-and-tubulo-interstitial-nephropathy
#17
Lin Chen, Dan-Qian Chen, Ming Wang, Dan Liu, Hua Chen, Fang Dou, Nosratola D Vaziri, Ying-Yong Zhao
Renin-angiotensin system (RAS) plays a key role in the development and progression of chronic kidney disease (CKD). Recent studies have demonstrated activation of Wnt/β-catenin pathway by RAS in CKD. However, the underlying mechanisms of RAS and Wnt/β-catenin signaling interaction and their contribution to the pathogenesis of CKD have not been fully elucidated. Present study is designed to investigate the role of RAS/Wnt/β-catenin axis activation in tubulo-interstitial fibrosis and glomerulosclerosis by the cultured HK-2 and podocytes...
June 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28578348/tlr4-influences-hepatitis-b-virus-related-hepatocellular-carcinoma-by-regulating-the-wnt-%C3%AE-catenin-pathway
#18
Yuanqin Yin, Fei Li, Songlin Li, Jingjing Cai, Jing Shi, Youhong Jiang
BACKGROUND/AIMS: We investigated the correlation between toll-like receptor 4 (TLR4) and β-catenin for disclosing the potential pathogenesis of hepatocellular carcinoma (HCC). METHODS: Immunohistochemical toolkit was implemented to measure the expression of TLR4 and β-catenin in 98 cases of HCC tissues and adjacent tissues. After setting up the HepG2.2.15 hepatitis B virus (HBV) related HCC cell line, we divided the cells into the control group, TLR4 siRNA group, β-catenin siRNA group, and pcDNA...
June 5, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28559284/the-autism-linked-ube3a-t485a-mutant-e3-ubiquitin-ligase-activates-the-wnt-%C3%AE-catenin-pathway-by-inhibiting-the-proteasome
#19
Jason J Yi, Smita R Paranjape, Matthew P Walker, Rajarshi Choudhury, Justin M Wolter, Giulia Fragola, Michael J Emanuele, Michael B Major, Mark J Zylka
UBE3A is a HECT domain E3 ubiquitin ligase whose dysfunction is linked to autism, Angelman syndrome, and cancer. Recently, we characterized a de novo autism-linked UBE3A mutant (UBE3AT485A) that disrupts phosphorylation control of UBE3A activity. Through quantitative proteomics and reporter assays, we found that the UBE3AT485A protein ubiquitinates multiple proteasome subunits, reduces proteasome subunit abundance and activity, stabilizes nuclear β-catenin, and stimulates canonical Wnt signaling more effectively than wild-type UBE3A...
May 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28553956/autocrine-wnt2-signaling-in-fibroblasts-promotes-colorectal-cancer-progression
#20
N Kramer, J Schmöllerl, C Unger, H Nivarthi, A Rudisch, D Unterleuthner, M Scherzer, A Riedl, M Artaker, I Crncec, D Lenhardt, T Schwarz, B Prieler, X Han, M Hengstschläger, J Schüler, R Eferl, R Moriggl, W Sommergruber, H Dolznig
The canonical WNT signaling pathway is crucial for intestinal stem cell renewal and aberrant WNT signaling is an early event in colorectal cancer (CRC) development. Here, we show for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma. The impact of stromal WNT2 on carcinoma formation or progression was not addressed so far. Canonical WNT/β-catenin signaling was assessed using a 7TGP-reporter construct. Furthermore, effects of WNT2 on fibroblast migration and invasion were determined using siRNA-mediated gene silencing...
May 29, 2017: Oncogene
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