Read by QxMD icon Read


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
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)...
June 16, 2016: Oncotarget
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
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
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
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
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
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
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
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
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
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
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
Suhail Ahmed Kabeer Rasheed, Cui Rong Teo, Emmanuel Jean Beillard, P Mathijs Voorhoeve, Wei Zhou, Sujoy Ghosh, Patrick J Casey
BACKGROUND: Gα13 (GNA13) is the α subunit of a heterotrimeric G protein that mediates signaling through specific G protein-coupled receptors (GPCRs). Our recent study showed that control of GNA13 expression by specific microRNAs (miRNAs or miRs) is important for prostate cancer cell invasion. However, little is known about the control of GNA13 expression in breast cancers. This project was carried out to determine (i) whether enhanced GNA13 expression is important for breast cancer cell invasion, and (ii) if so, the mechanism of deregulation of GNA13 expression in breast cancers...
2015: Molecular Cancer
Jagan R Muppidi, Roland Schmitz, Jesse A Green, Wenming Xiao, Adrien B Larsen, Sterling E Braun, Jinping An, Ying Xu, Andreas Rosenwald, German Ott, Randy D Gascoyne, Lisa M Rimsza, Elias Campo, Elaine S Jaffe, Jan Delabie, Erlend B Smeland, Rita M Braziel, Raymond R Tubbs, J R Cook, Dennis D Weisenburger, Wing C Chan, Nagarajan Vaidehi, Louis M Staudt, Jason G Cyster
Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7)...
December 11, 2014: Nature
J X Zhang, S J Mai, X X Huang, F W Wang, Y J Liao, M C Lin, H F Kung, Y X Zeng, D Xie
BACKGROUND: Distant metastasis is the major cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) has a critical role in this process. Accumulating evidence indicates that EMT can be regulated by microRNAs (miRNAs). miR-29c has been implicated as a tumor suppressor in several human cancers. However, the role of miR-29c in the progression of colorectal cancer (CRC) metastasis remains largely unknown. PATIENTS AND METHODS: The expression of miR-29c was examined by qRT-PCR in a cohort of primary CRC (PC) and distant liver metastasis (LM) tissues...
November 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Brian Patrick O'Neill, E Braggio, B P O'Neill, S Van Wier, J Ojha, E McPhail, Y Asmann, J Egan, J Ayres da Silva, D Schiff, M B Lopes, R Valdez, R Tibes, B Eckloff, A K Stewart, R Fonseca
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma (NHL) confined to the CNS. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic DLBCL is uncertain. To address this gap in critical knowledge we performed a comprehensive genomic study in a cohort of 19 immunocompetent PCNSL patients by combining aCGH, whole exome sequencing and mate-pair whole genome sequencing. METHODS: 1) Tumor samples from 19 immunocompetent (HIV-, EBV-) PCNSL...
July 2014: Neuro-oncology
Crystal Y Chia, Udhaya Kumari, Patrick J Casey
BACKGROUND: Recent studies on the involvement of the G12 family of heterotrimeric G proteins (Gα12 and Gα13, the products of the GNA12 and GNA13 genes, respectively) in oncogenic pathways have uncovered a link between G12 signaling and cancer progression. However, despite a well characterized role of Rho GTPases, the potential role of secreted factors in the capacity of G12 signaling to promote invasion of cancer cells is just beginning to be addressed. METHODS: MDA-MB-231 and MCF10A breast cancer cell lines were employed as a model system to explore the involvement of secreted factors in G12-stimulated cell invasion...
2014: Journal of Molecular Signaling
Adrienne Greenough, Sandeep S Dave
PURPOSE OF REVIEW: Burkitt lymphoma is an important clinical and model disease arising from B cells. Burkitt lymphoma is characterized by translocation of the c-MYC gene to an immunoglobulin enhancer region, resulting in enhanced cell proliferation and rapid tumor progression. The development of deep sequencing has widened the scope of genetic analysis to reveal the role of additional collaborating mutations in Burkitt lymphoma. In this review, we examine the role of additional genetic events that cooperate with MYC in Burkitt lymphoma pathogenesis...
July 2014: Current Opinion in Hematology
Emma Sprooten, Emma E Knowles, D Reese McKay, Harald H Göring, Joanne E Curran, Jack W Kent, Melanie A Carless, Thomas D Dyer, Eugene I Drigalenko, Rene L Olvera, Peter T Fox, Laura Almasy, Ravi Duggirala, Peter Kochunov, John Blangero, David C Glahn
Identifying genes that contribute to white matter microstructure should provide insights into the neurobiological processes that regulate white matter development, plasticity and pathology. We detected five significant SNPs using genome-wide association analysis on a global measure of fractional anisotropy in 776 individuals from large extended pedigrees. Genetic correlations and genome-wide association results indicated that the genetic signal was largely homogeneous across white matter regions. Using RNA transcripts derived from lymphocytes in the same individuals, we identified two genes (GNA13 and CCDC91) that are likely to be cis-regulated by top SNPs, and whose expression levels were also genetically correlated with fractional anisotropy...
August 15, 2014: NeuroImage
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"