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https://www.readbyqxmd.com/read/28394299/c-jun-contributes-to-transcriptional-control-of-gna12-expression-in-prostate-cancer-cells
#1
Udhaya Kumari Udayappan, Patrick J Casey
Abstract: GNA12 is the α subunit of a heterotrimeric G protein that possesses oncogenic potential. Activated GNA12 also promotes prostate and breast cancer cell invasion in vitro and in vivo, and its expression is up-regulated in many tumors, particularly metastatic tissues. In this study, we explored the control of expression of GNA12 in prostate cancer cells. Initial studies on LnCAP (low metastatic potential, containing low levels of GNA12) and PC3 (high metastatic potential, containing high GNA12 levels) cells revealed that GNA12 mRNA levels correlated with protein levels, suggesting control at the transcriptional level...
April 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28302137/mutations-of-crebbp-and-socs1-are-independent-prognostic-factors-in-diffuse-large-b-cell-lymphoma-mutational-analysis-of-the-sakk-38-07-prospective-clinical-trial-cohort
#2
Darius Juskevicius, David Jucker, Dirk Klingbiel, Christoph Mamot, Stephan Dirnhofer, Alexandar Tzankov
BACKGROUND/PURPOSE: Recently, the mutational background of diffuse large B cell lymphoma (DLBCL) has been revealed, identifying specific genetic events that drive lymphomagenesis. However, the prognostic value of these mutations remains to be determined. Prognostic biomarkers in DLBCL are urgently needed, since the current clinical parameter-based factors (e.g., International Prognostic Index (IPI)) are insufficient, particularly in identifying patients with poor prognosis who might benefit from alternative treatments...
March 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28214564/downregulation-of-gna13-erk-network-in-prefrontal-cortex-of-schizophrenia-brain-identified-by-combined-focused-and-targeted-quantitative-proteomics
#3
Mio Hirayama-Kurogi, Yohei Takizawa, Yasuto Kunii, Junya Matsumoto, Akira Wada, Mizuki Hino, Hiroyasu Akatsu, Yoshio Hashizume, Sakon Yamamoto, Takeshi Kondo, Shingo Ito, Masanori Tachikawa, Shin-Ichi Niwa, Hirooki Yabe, Tetsuya Terasaki, Mitsutoshi Setou, Sumio Ohtsuki
Schizophrenia is a disabling mental illness associated with dysfunction of the prefrontal cortex, which affects cognition and emotion. The purpose of the present study was to identify altered molecular networks in the prefrontal cortex of schizophrenia patients by comparing protein expression levels in autopsied brains of patients and controls, using a combination of targeted and focused quantitative proteomics. We selected 125 molecules possibly related to schizophrenia for quantification by knowledge-based targeted proteomics...
February 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28117656/epigenetic-profiling-of-human-brain-differential-dna-methylation-networks-in-schizophrenia
#4
Sheng-An Lee, Kuo-Chuan Huang
BACKGROUND: Epigenetics of schizophrenia provides important information on how the environmental factors affect the genetic architecture of the disease. DNA methylation plays a pivotal role in etiology for schizophrenia. Previous studies have focused mostly on the discovery of schizophrenia-associated SNPs or genetic variants. As postmortem brain samples became available, more and more recent studies surveyed transcriptomics of the diseases. In this study, we constructed protein-protein interaction (PPI) network using the disease associated SNP (or genetic variants), differentially expressed disease genes and differentially methylated disease genes (or promoters)...
December 5, 2016: BMC Medical Genomics
https://www.readbyqxmd.com/read/28102206/g%C3%AE-13-negatively-controls-osteoclastogenesis-through-inhibition-of-the-akt-gsk3%C3%AE-nfatc1-signalling-pathway
#5
Mengrui Wu, Wei Chen, Yun Lu, Guochun Zhu, Liang Hao, Yi-Ping Li
Many positive signalling pathways of osteoclastogenesis have been characterized, but negative signalling pathways are less well studied. Here we show by microarray and RNAi that guanine nucleotide-binding protein subunit α13 (Gα13) is a negative regulator of osteoclastogenesis. Osteoclast-lineage-specific Gna13 conditional knockout mice have a severe osteoporosis phenotype. Gna13-deficiency triggers a drastic increase in both osteoclast number and activity (hyper-activation), mechanistically through decreased RhoA activity and enhanced Akt/GSK3β/NFATc1 signalling...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/27959929/histological-transformation-and-progression-in-follicular-lymphoma-a-clonal-evolution-study
#6
Robert Kridel, Fong Chun Chan, Anja Mottok, Merrill Boyle, Pedro Farinha, King Tan, Barbara Meissner, Ali Bashashati, Andrew McPherson, Andrew Roth, Karey Shumansky, Damian Yap, Susana Ben-Neriah, Jamie Rosner, Maia A Smith, Cydney Nielsen, Eva Giné, Adele Telenius, Daisuke Ennishi, Andrew Mungall, Richard Moore, Ryan D Morin, Nathalie A Johnson, Laurie H Sehn, Thomas Tousseyn, Ahmet Dogan, Joseph M Connors, David W Scott, Christian Steidl, Marco A Marra, Randy D Gascoyne, Sohrab P Shah
BACKGROUND: Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27883022/high-expression-of-gna13-is-associated-with-poor-prognosis-in-hepatocellular-carcinoma
#7
Yi Xu, Jian Rong, Shiyu Duan, Cui Chen, Yin Li, Baogang Peng, Bin Yi, Zhousan Zheng, Ying Gao, Kebing Wang, Miao Yun, Huiwen Weng, Jiaxing Zhang, Sheng Ye
Guanine nucleotide binding protein alpha 13 (GNA13) has been found to play critical roles in the development of several human cancers. However, little is known about GNA13 expression and its clinical significance in hepatocellular carcinoma (HCC). In our study, GNA13 was reported to be significantly up-regulated in HCC tissues, and this was correlated with several clinicopathological parameters, including tumor multiplicity (P = 0.004), TNM stage (P = 0.002), and BCLC stage (P = 0.010). Further Cox regression analysis suggested that GNA13 expression was an independent prognostic factor for overall survival (P = 0...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27424208/the-gna13-rhoa-signaling-axis-suppresses-expression-of-tumor-protective-kallikreins
#8
Cui Rong Teo, Patrick J Casey, Suhail Ahmed Kabeer Rasheed
Gα13 (encoded by GNA13 gene) is the alpha subunit of a heterotrimeric G-protein that mediates signaling through specific G-protein-coupled receptors (GPCRs). Increased GNA13 expression has been observed in metastatic breast cancer cells. Recently, we have shown that enhanced GNA13 signaling in MCF-10a cells, a benign breast cancer cell line increased its invasiveness. Previous studies have reported that Kallikrein-related peptidases (KLKs 1-15) are down-regulated in breast tumors and may have a tumor protective function...
October 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27331623/the-melanoma-enriched-microrna-mir-4731-5p-acts-as-a-tumour-suppressor
#9
Mitchell S Stark, Lisa N Tom, Glen M Boyle, Vanessa F Bonazzi, H Peter Soyer, Adrian C Herington, Pamela M Pollock, Nicholas K Hayward
We previously identified miR-4731-5p (miR-4731) as a melanoma-enriched microRNA following comparison of melanoma with other cell lines from solid malignancies. Additionally, miR-4731 has been found in serum from melanoma patients and expressed less abundantly in metastatic melanoma tissues from stage IV patients relative to stage III patients. As miR-4731 has no known function, we used biotin-labelled miRNA duplex pull-down to identify binding targets of miR-4731 in three melanoma cell lines (HT144, MM96L and MM253)...
August 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/26989201/gna13-loss-in-germinal-center-b-cells-leads-to-impaired-apoptosis-and-promotes-lymphoma-in-vivo
#10
Jane A Healy, Adrienne Nugent, Rachel E Rempel, Andrea B Moffitt, Nicholas S Davis, Xiaoyu Jiang, Jennifer R Shingleton, Jenny Zhang, Cassandra Love, Jyotishka Datta, Matthew E McKinney, Tiffany J Tzeng, Nina Wettschureck, Stefan Offermanns, Katelyn A Walzer, Jen-Tsan Chi, Suhail A K Rasheed, Patrick J Casey, Izidore S Lossos, Sandeep S Dave
GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13 conditional knockout mouse strain with the GC-specific AID-Cre transgenic strain. AID-Cre(+) GNA13-deficient mice demonstrate disordered GC architecture and dark zone/light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro...
June 2, 2016: Blood
https://www.readbyqxmd.com/read/26819451/next-generation-sequencing-in-diffuse-large-b-cell-lymphoma-highlights-molecular-divergence-and-therapeutic-opportunities-a-lysa-study
#11
Sydney Dubois, Pierre-Julien Viailly, Sylvain Mareschal, Elodie Bohers, Philippe Bertrand, Philippe Ruminy, Catherine Maingonnat, Jean-Philippe Jais, Pauline Peyrouze, Martin Figeac, Thierry J Molina, Fabienne Desmots, Thierry Fest, Corinne Haioun, Thierry Lamy, Christiane Copie-Bergman, Josette Brière, Tony Petrella, Danielle Canioni, Bettina Fabiani, Bertrand Coiffier, Richard Delarue, Frédéric Peyrade, André Bosly, Marc André, Nicolas Ketterer, Gilles Salles, Hervé Tilly, Karen Leroy, Fabrice Jardin
PURPOSE: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials. EXPERIMENTAL DESIGN: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients...
June 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26804165/gep-oncogene-promotes-cell-proliferation-through-yap-activation-in-ovarian-cancer
#12
H Yagi, K Asanoma, T Ohgami, A Ichinoe, K Sonoda, K Kato
G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. Gα12 and Gα13, encoded by GNA12 and GNA13, respectively, are referred to as the GEP oncogene and are implicated in tumor progression. However, the molecular mechanisms by which Gα12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of Gα12/13 in human ovarian cancer tissues. Gα12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined...
August 25, 2016: Oncogene
https://www.readbyqxmd.com/read/26773040/diffuse-large-b-cell-lymphoma-patient-derived-xenograft-models-capture-the-molecular-and-biological-heterogeneity-of-the-disease
#13
Bjoern Chapuy, Hongwei Cheng, Akira Watahiki, Matthew D Ducar, Yuxiang Tan, Linfeng Chen, Margaretha G M Roemer, Jing Ouyang, Amanda L Christie, Liye Zhang, Daniel Gusenleitner, Ryan P Abo, Pedro Farinha, Frederike von Bonin, Aaron R Thorner, Heather H Sun, Randy D Gascoyne, Geraldine S Pinkus, Paul van Hummelen, Gerald G Wulf, Jon C Aster, David M Weinstock, Stefano Monti, Scott J Rodig, Yuzhuo Wang, Margaret A Shipp
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease defined by transcriptional classifications, specific signaling and survival pathways, and multiple low-frequency genetic alterations. Preclinical model systems that capture the genetic and functional heterogeneity of DLBCL are urgently needed. Here, we generated and characterized a panel of large B-cell lymphoma (LBCL) patient-derived xenograft (PDX) models, including 8 that reflect the immunophenotypic, transcriptional, genetic, and functional heterogeneity of primary DLBCL and 1 that is a plasmablastic lymphoma...
May 5, 2016: Blood
https://www.readbyqxmd.com/read/26735177/gna13-as-a-prognostic-factor-and-mediator-of-gastric-cancer-progression
#14
COMPARATIVE STUDY
Jia-Xing Zhang, Miao Yun, Yi Xu, Jie-Wei Chen, Hui-Wen Weng, Zou-San Zheng, Cui Chen, Dan Xie, Sheng Ye
Guanine nucleotide binding protein (G protein), alpha 13 (GNA13) has been implicated as an oncogenic protein in several human cancers. In this study, GNA13 was characterized for its role in gastric cancer (GC) progression and underlying molecular mechanisms. The expression dynamics of GNA13 were examined by immunohistochemistry (IHC) in two independent cohorts of GC samples. A series of in-vivo and in-vitro assays was performed to elucidate the function of GNA13 in GC and its underlying mechanisms. In both two cohorts of GC samples, we observed that GNA13 was markedly overexpressed in GC tissues and associated closely with aggressive magnitude of GC progression and poor patients' survival...
January 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26616858/inactivating-mutations-in-gna13-and-rhoa-in-burkitt-s-lymphoma-and-diffuse-large-b-cell-lymphoma-a-tumor-suppressor-function-for-the-g%C3%AE-13-rhoa-axis-in-b-cells
#15
M O'Hayre, A Inoue, I Kufareva, Z Wang, C M Mikelis, R A Drummond, S Avino, K Finkel, K W Kalim, G DiPasquale, F Guo, J Aoki, Y Zheng, M S Lionakis, A A Molinolo, J S Gutkind
G proteins and their cognate G protein-coupled receptors (GPCRs) function as critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression and/or function of these molecules have been linked to the growth, progression and metastasis of various cancers. As such, the analysis of mutations in the genes encoding GPCRs, G proteins and their downstream targets provides important clues regarding how these signaling cascades contribute to malignancy...
July 21, 2016: Oncogene
https://www.readbyqxmd.com/read/26608593/whole-exome-sequencing-of-relapsed-refractory-patients-expands-the-repertoire-of-somatic-mutations-in-diffuse-large-b-cell-lymphoma
#16
Sylvain Mareschal, Sydney Dubois, Pierre-Julien Viailly, Philippe Bertrand, Elodie Bohers, Catherine Maingonnat, Jean-Philippe Jaïs, Bruno Tesson, Philippe Ruminy, Pauline Peyrouze, Christiane Copie-Bergman, Thierry Fest, Thierry Jo Molina, Corinne Haioun, Gilles Salles, Hervé Tilly, Thierry Lecroq, Karen Leroy, Fabrice Jardin
Despite the many efforts already spent to enumerate somatic mutations in diffuse large B-cell lymphoma (DLBCL), previous whole-genome and whole-exome studies conducted on patients of mixed outcomes failed at characterizing the 30% of patients who will relapse or resist current immunochemotherapies. To address this issue, we performed whole-exome sequencing of normal/tumoral DNA pairs in 14 relapsed/refractory (R/R) patients subclassified by full-transcriptome arrays (six activated B-cell like, three germinal center B-cell like, and five primary mediastinal B-cell lymphomas), from the LNH-03 LYSA clinical trial program...
March 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/26573295/the-g-protein-coupled-receptor-p2ry8-and-follicular-dendritic-cells-promote-germinal-center-confinement-of-b-cells-whereas-s1pr3-can-contribute-to-their-dissemination
#17
Jagan R Muppidi, Erick Lu, Jason G Cyster
The orphan Gα13-coupled receptor P2RY8 is mutated in human germinal center (GC)-derived lymphomas and was recently found to promote B cell association with GCs in a mouse model. Here we establish that P2RY8 promotes clustering of activated B cells within follicles in a follicular dendritic cell (FDC)-dependent manner. Although mice lack a P2RY8 orthologue, we show that mouse GC B cell clustering is also dependent on FDCs acting to support the function of a Gα13-coupled receptor. Mutations in GNA13 and its downstream effector ARHGEF1 are associated with the development of disseminated GC-derived lymphomas...
December 14, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26567765/the-presence-of-genomic-imbalances-is-associated-with-poor-outcome-in-patients-with-burkitt-lymphoma-treated-with-dose-intensive-chemotherapy-including-rituximab
#18
Maribel Forero-Castro, Cristina Robledo, Eva Lumbreras, Rocio Benito, Jesús M Hernández-Sánchez, María Hernández-Sánchez, Juan L García, Luis A Corchete-Sánchez, Mar Tormo, Pere Barba, Javier Menárguez, Jordi Ribera, Carlos Grande, Lourdes Escoda, Carmen Olivier, Estrella Carrillo, Alfonso García de Coca, Josep-María Ribera, Jesús M Hernández-Rivas
The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization (CGH)...
February 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/26323264/rgs22-inhibits-pancreatic-adenocarcinoma-cell-migration-through-the-g12-13-%C3%AE-subunit-f-actin-pathway
#19
Yanqiu Hu, Jun Xing, Ling Chen, Ying Zheng, Zuomin Zhou
Pancreatic cancer is characterized by the potential for local invasion, allowing it to spread during the early developmental stages of the disease. Regulator of G protein signaling 22 (RGS22) localizes to the cytoplasm in pancreatic adenocarcinoma tissue. We overexpressed RGS22 in the human pancreatic cancer cell line BXPC-3. Cells that overexpressed RGS22 had much lower wound-healing rates and greatly reduced migration compared to the control cells. Conversely, cells in which RGS22 expression had been downregulated had higher wound-healing rates and migration than the control cells...
November 2015: Oncology Reports
https://www.readbyqxmd.com/read/25991819/genome-wide-analysis-uncovers-novel-recurrent-alterations-in-primary-central-nervous-system-lymphomas
#20
Esteban Braggio, Scott Van Wier, Juhi Ojha, Ellen McPhail, Yan W Asmann, Jan Egan, Jackline Ayres da Silva, David Schiff, M Beatriz Lopes, Paul A Decker, Riccardo Valdez, Raoul Tibes, Bruce Eckloff, Thomas E Witzig, A Keith Stewart, Rafael Fonseca, Brian Patrick O'Neill
PURPOSE: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the central nervous system. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain. EXPERIMENTAL DESIGN: We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing...
September 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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