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Molecular Cancer Research: MCR

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https://www.readbyqxmd.com/read/28522693/histone-h3-3k27m-represses-p16-to-accelerate-gliomagenesis-in-a-murine-model-of-dipg
#1
Francisco J Cordero, Zhiqing Huang, Carole Grenier, Xingyao He, Guo Hu, Roger E McLendon, Susan K Murphy, Rintaro Hashizume, Oren J Becher
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date the tumor-driving effects of H3...
May 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28512253/infiltrating-myeloid-cells-exert-pro-tumorigenic-actions-via-neutrophil-elastase
#2
Irina Lerman, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Luis Chiriboga, Chunliu Pan, Kent L Nastiuk, John J Krolewski, Aritro Sen, Stephen R Hammes
Tissue infiltration and elevated peripheral circulation of granulocytic myeloid-derived cells is associated with poor outcomes in prostate cancer (PCa) and other malignancies. Although myeloid-derived cells have the ability to suppress T-cell function, little is known about the direct impact of these innate cells on prostate tumor growth. Here it is reported that granulocytic myeloid-derived suppressor cells (MDSCs) are the predominant tumor infiltrating cells in PCa xenografts established in athymic nude mice...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28512252/epigenetic-regulation-of-zbtb18-promotes-glioblastoma-progression
#3
Vita Fedele, Fangping Dai, Anie Masilamani, Dieter Henrik Heiland, Eva Kling, Ana Gätjens-Sanchez, Roberto Ferrarese, Leonardo Platania, Soroush Doostkam, Hyunsoo Kim, Sven Nelander, Astrid Weyerbrock, Marco Prinz, Andrea Califano, Antonio Iavarone, Markus Bredel, Maria Stella Carro
Glioblastoma (GBM) is comprised of distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28512251/inhibition-of-the-cell-death-pathway-in-non-alcoholic-steatohepatitis-nash-related-hepatocarcinogenesis-is-associated-with-histone-h4-lysine-16-deacetylation
#4
Aline de Conti, Kostiantyn Dreval, Volodymyr Tryndyak, Orish Ebere Orisakwe, Sharon Ross, Frederick Beland, Igor P Pogribny
Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers and its incidence is steadily increasing worldwide. Recent epidemiological findings have suggested that the increased incidence of HCC is associated with obesity, type 2 diabetes mellitus, and nonalcoholic steatohepatitis (NASH); however, the mechanisms and the molecular pathogenesis of NASH-related HCC are not fully understood. In order to elucidate the underlying mechanisms of the development of NASH-related HCC, we investigated the hepatic transcriptomic and histone modification profiles in Stelic Animal Model (STAM) mice, the first animal model of NASH-related HCC to resemble the disease pathogenesis in humans...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28507054/glutamine-transporters-are-targets-of-multiple-oncogenic-signaling-pathways-in-prostate-cancer
#5
Mark A White, Chenchu Lin, Kimal Rajapakshe, Jianrong Dong, Yan Shi, Efrosini Tsouko, Ratna Mukhopadhyay, Diana Jasso, Wajahat Dawood, Cristian Coarfa, Daniel E Frigo
Despite the known importance of androgen receptor (AR) signaling in prostate cancer (PCa), the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in PCa cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in PCa...
May 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28487380/egfr-signals-through-a-dock180-mlk3-axis-to-drive-glioblastoma-cell-invasion
#6
Sean Misek, Jian Chen, Laura Schroeder, Chotirat Rattanasinchai, Ashley Sample, Jann N Sarkaria, Kathleen A Gallo
A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that control GBM cell dissemination is critical for developing effective therapies to treat GBM. A majority of GBM tumors have dysregulated EGFR signaling, due most frequently to EGFR amplification or the presence of a constitutively active EGFRvIII mutant. Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that can activate multiple MAPK pathways...
May 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28483948/high-affinity-internalizing-human-scfv-fc-antibody-for-targeting-fgfr1-overexpressing-lung-cancer
#7
Aleksandra Sokolowska-Wedzina, Grzegorz Chodaczek, Julia Chudzian, Aleksandra Borek, Malgorzata Zakrzewska, Jacek Otlewski
Targeted delivery of anti-cancer drugs using antibodies specific for tumor-associated antigens represents one of the most important approaches in current immuno-oncology research. Fibroblast growth factor receptor 1 (FGFR1) has been demonstrated to be a high-frequency targetable oncogene specific for smoking-associated lung cancers, present in over 20% of lung squamous cell carcinoma cases. This report describes the generation of a potent, fully human antibody fragment in scFv-Fc format efficiently targeting FGFR1...
May 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28483947/regulation-of-usp37-expression-by-rest-associated-g9a-dependent-histone-methylation
#8
Tara Dobson, Rashieda J Hatcher, Jyothismathi Swaminathan, Chandra M Das, Shavali Shaik, Rong-Hua Tao, Ciro Milite, Sabrina Castellano, Pete Taylor, Gianluca Sbardella, Vidya Gopalakrishnan
The deubiquitylase (DUB) USP37 is a component of the ubiquitin system and controls cell proliferation by regulating the stability of the cyclin-dependent kinase inhibitor 1B, (CDKN1B/p27Kip1). The expression of USP37 is down-regulated in human medulloblastoma tumor specimens. In the current study we show that USP37 prevents medulloblastoma growth in mouse orthotopic models, suggesting that it has tumor suppressive properties in this neural cancer. Here, we also report on the mechanism underlying USP37 loss in medulloblastoma...
May 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28483946/p53-maintains-baseline-expression-of-multiple-tumor-suppressor-genes
#9
Kyrie Pappas, Jia Xu, Sakellarios Zairis, Lois Resnick-Silverman, Francesco Abate, Nicole Steinbach, Sait Ozturk, Lao H Saal, Tao Su, Pamela Cheung, Hank Schmidt, Stuart A Aaronson, Hanina Hibshoosh, James J Manfredi, Raul Rabadan, Ramon Parsons
TP53 is the most commonly mutated tumor suppressor gene and its mutation drives tumorigenesis. Using ChIP-seq for p53 in the absence of acute cell stress, we found that wild-type but not mutant p53 binds and activates numerous tumor suppressor genes including PTEN, STK11(LKB1), miR-34a, KDM6A(UTX), FOXO1, PHLDA3, and TNFRSF10B through consensus binding sites in enhancers and promoters. Depletion of p53 reduced expression of these target genes, and analysis across 18 tumor types showed that mutation of TP53 associated with reduced expression of many of these genes...
May 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28461326/eif2%C3%AE-phosphorylation-mediates-il24-induced-apoptosis-through-inhibition-of-translation
#10
Leah Persaud, Xuelin Zhong, Giselle Alvarado, Winchie Do, Jordan Dejoie, Anna Zybtseva, Bertal H Aktas, Moira Sauane
Interleukin 24 (IL-24) is an immunomodulatory cytokine that also displays broad cancer-specific suppressor effects. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, sensitization to chemotherapy, and cancer-specific apoptosis. Supra-physiologic activation and/or overexpression of translation initiation factors are implicated in the initiation and progression of cancer animal models as well as a subset of human cancers. Activation and/or overexpression of translation initiation factors correlate with aggressiveness of cancer and poor prognosis...
May 1, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28461325/role-of-rac1-pathway-in-epithelial-to-mesenchymal-transition-and-cancer-stem-like-cell-phenotypes-in-gastric-adenocarcinoma
#11
Changhwan Yoon, Soo-Jeong Cho, Kevin K Chang, Do Joong Park, Sandra Ryeom, Sam S Yoon
Rac1, a Rho GTPase family member, is dysregulated in a variety of tumor types including gastric adenocarcinoma (GA), but little is known about its role in cancer stem-like cells (CSCs). Therefore, Rac1 activity and inhibition were examined in GA cells and mouse xenograft models for epithelial-to-mesenchymal transition (EMT) and CSC phenotypes. Rac1 activity was significantly higher in spheroid-forming or CD44(+) GA CSCs compared to unselected cells. Rac1 inhibition using Rac1 shRNA or a Rac1 inhibitor (NSC23766) decreased expression of the self-renewal transcription factor, Sox-2, decreased spheroid formation by 78-81%, and prevented tumor initiation in immunodeficient mice...
May 1, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28442587/combined-aurka-and-h3k9-methyltransferase-targeting-inhibits-cell-growth-by-inducing-mitotic-catastrophe
#12
Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Jennifer Bintz, Monique Williams, Sarah Kossak, Asha Nair, Thiago M de Assuncao, Trace A Christensen, Navtej S Buttar, Juan L Iovanna, Robert Huebert, Gwen Lomberk
The current integrative pathobiological hypothesis states that pancreatic cancer (PDAC) develops and progresses in response to an interaction between known oncogenes and downstream epigenomic regulators. Congruently, this study tests a new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA) oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway. This therapeutic combination is effective at inhibiting the in vitro growth of PDAC cells both, in monolayer culture systems, and in 3D spheroids and organoids...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28442586/therapeutic-targeting-of-ptk7-is-cytotoxic-in-atypical-teratoid-rhabdoid-tumors
#13
Shanta M Messerli, Mariah M Hoffman, Etienne Z Gnimpieba, Ratan D Bhardwaj
Novel discoveries involving the evaluation of potential therapeutics are based on newly identified molecular targets for atypical teratoid rhabdoid tumors (ATRT), which are the most common form of infantile brain tumors. Central nervous system ATRTs are rare, aggressive, and fast growing tumors of the brain and spinal cord and carry a very poor prognosis. Currently, the standard of care for ATRT patients is based on surgical resection followed by systemic chemotherapy and radiation therapy, which result in severe side effects...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28442585/next-gen-sequencing-analysis-and-algorithms-for-pdx-and-cdx-models
#14
Garima Khandelwal, Maria Romina Girotti, Christopher Smowton, Sam Taylor, Chris Wirth, Marek Dynowski, Kristopher K Frese, Ged Brady, Caroline Dive, Richard Marais, Crispin Miller
Patient-derived xenograft (PDX) and CTC-derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these methods have been applied to multiple questions including the study of metastatic progression, genetic evolution and therapeutic drug responses. Since PDX and CDX models can recapitulate the highly heterogeneous characteristics of a patient tumor, as well as their response to chemotherapy, there is considerable interest in combining them with next-generation sequencing (NGS) in order to monitor the genomic, transcriptional, and epigenetic changes that accompany oncogenesis...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28396463/blind-selex-approach-identifies-rna-aptamer-that-regulate-emt-and-inhibit-metastasis
#15
Sorah Yoon, Brian Armstrong, Nagy Habib, John J Rossi
Identifying targets that are exposed on the plasma membrane of tumor cells, but expressed internally in normal cells, is a fundamental issue for improving the specificity and efficacy of anticancer therpeutics. Using blind cell SELEX (Systemic Evolution of Ligands by EXponetial enrichment) which is untargeted SELEX, we have identified an aptamer, P15, which specifically bound to the human pancreatic adenocarcinoma cells. To identify the aptamer binding plasma membrane protein, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used...
April 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28396462/lncrna-gas5-inhibits-cellular-proliferation-by-targeting-p27kip1
#16
Gang Luo, Dong Liu, Chao Huang, Miao Wang, Xingyuan Xiao, Fuqing Zeng, Liang Wang, Guosong Jiang
Recent studies have demonstrated that long non-coding RNAs (lncRNAs) have important roles in cancer biology, and that the downregulation of lncRNA growth arrest-specific transcript 5 (GAS5) has been reported in a variety of human cancers. However, its role in prostate cancer is largely unknown. This study aims investigated the biological role and underlying mechanism of GAS5 on proliferation in prostate cancer. The results demonstrate that GAS5 expression is significantly decreased in prostate cancer cells compared with prostate epithelial cells...
April 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28389619/differential-expression-of-oatp1b3-mediates-unconjugated-testosterone-influx
#17
Tristan M Sissung, Ariel M Ley, Jonathan D Strope, Edel M McCrea, Shaunna L Beedie, Cody J Peer, Suneet Shukla, Jennifer C van Velkinburgh, Kelie Reece, Sarah Troutman, Tessa Campbell, Elena Fernandez, Phoebe Huang, Jordan Smith, Nilay Thakkar, David Venzon, Steffan Brenner, Wooin Lee, Maria J Merino, Ji Luo, Walter Jager, Cindy H Chau, Douglas K Price, William D Figg
Castration resistant prostate cancer (CRPC) has greater intratumoral testosterone concentrations than similar tumors from eugonadal men; simple diffusion does not account for this observation. The present study was undertaken to ascertain the androgen uptake kinetics, functional, and clinical relevance of de novo expression of the steroid hormone transporter OATP1B3 (SLCO1B3). Experiments testing the cellular uptake of androgens suggest that testosterone is an excellent substrate of OATP1B3 (KM=23.2µM; VMAX=321...
April 7, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28385910/metformin-reduces-prostate-tumor-growth-in-a-diet-dependent-manner-by-modulating-multiple-signaling-pathways
#18
Andre Sarmento-Cabral, Fernando L-Lopez, Manuel D Gahete, Justo P Castano, Raul M Luque
Prostate-cancer is strongly influenced by obesity, wherein metformin could represent a promising treatment; however, the endocrine-metabolic/cellular/molecular-mechanisms underlying these associations and effects are still unclear. To determine the beneficial anti-tumoral effects of metformin on prostate-cancer progression/aggressiveness and the relative contribution of high-fat diet (HFD; independently of obesity), we used HFD-fed immuno-suppressed mice inoculated with PC3 cells (which exhibited partial resistance to diet-induced obesity) compared with low-fat diet (LFD)-fed control-mice...
April 6, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28373289/mir-202-diminishes-tgfbeta-receptors-and-attenuates-tgfbeta1-induced-emt-in-pancreatic-cancer
#19
Hardik Mody, Sau Wai Hung, Rakesh Pathak, Jazmine Griffin, Zobeida Cruz-Monserrate, Rajgopal Govindarajan
Previous studies in our laboratory identified that 3-deazaneplanocin A (DZNep), a carbocyclic adenosine analog and histone methyl transferase inhibitor, suppresses TGFβ-induced epithelial-to-mesenchymal (EMT) characteristics. In addition, DZNep epigenetically reprograms miRNAs (miRs) to regulate endogenous TGFbeta1 levels via miR-663/4787 mediated RNA interference (Mol Cancer Res. 2016 Sep 13. pii: molcanres.0083.2016) (1). While DZNep also attenuates exogenous TGFbeta-induced EMT response, the mechanism of this inhibition was unclear...
April 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28360038/insulin-receptor-and-gpcr-crosstalk-stimulates-yap-via-pi3k-and-pkd-in-pancreatic-cancer-cells
#20
Fang Hao, Qinhong Xu, Yinglan Zhao, Jan V Stevens, Steven H Young, James Sinnett-Smith, Enrique Rozengurt
We examined the impact of crosstalk between the insulin receptor and G protein-coupled receptor (GPCR) signaling pathways on the regulation of Yes-associated protein (YAP) localization, phosphorylation, and transcriptional activity in the context of human pancreatic ductal adenocarcinoma (PDAC). Stimulation of PANC-1 or MiaPaCa-2 cells with insulin and neurotensin, a potent mitogenic combination of agonists for these cells, promoted striking YAP nuclear localization and decreased YAP phosphorylation at Ser(127) and Ser(397) Challenging PDAC cells with either insulin or neurotensin alone modestly induced the expression of YAP/TEAD-regulated genes, including connective tissue growth factor (CTGF), cysteine-rich angiogenic inducer 61 (CYR61), and CXCL5, whereas the combination of neurotensin and insulin induced a marked increase in the level of expression of these genes...
March 30, 2017: Molecular Cancer Research: MCR
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