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Swi/snf complex

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https://www.readbyqxmd.com/read/29671892/frequent-loss-of-claudin-4-expression-in-dedifferentiated-and-undifferentiated-endometrial-carcinomas
#1
Basile Tessier-Cloutier, Robert A Soslow, Colin J R Stewart, Martin Köbel, Cheng-Han Lee
INTRO: Dedifferentiated/undifferentiated endometrial carcinomas (DDEC/UEC) are aggressive endometrial cancers with frequent genomic inactivation of core components of switch/sucrose non-fermentable (SWI/SNF) complex proteins. Claudin-4, an epithelial intercellular tight junction protein was recently found to be expressed in SWI/SNF-deficient undifferentiated carcinomas but not SWI/SNF-deficient sarcomas. The aim of this study is to examine claudin-4 expression in UEC/DDEC and other high-grade uterine carcinomas...
April 19, 2018: Histopathology
https://www.readbyqxmd.com/read/29650362/tazemetostat-an-ezh2-inhibitor-in-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma-and-advanced-solid-tumours-a-first-in-human-open-label-phase-1-study
#2
Antoine Italiano, Jean-Charles Soria, Maud Toulmonde, Jean-Marie Michot, Carlo Lucchesi, Andrea Varga, Jean-Michel Coindre, Stephen J Blakemore, Alicia Clawson, Benjamin Suttle, Alice A McDonald, Mark Woodruff, Scott Ribich, Eric Hedrick, Heike Keilhack, Blythe Thomson, Takashi Owa, Robert A Copeland, Peter T C Ho, Vincent Ribrag
BACKGROUND: Activating enhancer of zeste homolog 2 (EZH2) mutations or aberrations of the switch/sucrose non-fermentable (SWI/SNF) complex (eg, mutations or deletions of the subunits INI1 or SMARCA4) can lead to aberrant histone methylation, oncogenic transformation, and a proliferative dependency on EZH2 activity. In this first-in-human study, we aimed to investigate the safety, clinical activity, pharmacokinetics, and pharmacodynamics of tazemetostat, a first-in-class selective inhibitor of EZH2...
April 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29650150/the-swi-snf-subunit-swi3b-regulates-iamt1-expression-via-chromatin-remodeling-in-arabidopsis-leaf-development
#3
Wenxing Han, Danlu Han, Zhipeng He, Huan Hu, Qian Wu, Juanjuan Zhang, Jieming Jiang, Genji Qin, Yuhai Cui, Jianbin Lai, Chengwei Yang
The SWI/SNF complex is crucial to chromatin remodeling in various biological processes in different species, but the distinct functions of its components in plant development remain unclear. Here we uncovered the role of SWI3B, a subunit of the Arabidopsis thaliana SWI/SNF complex, via RNA interference. Knockdown of SWI3B resulted in an upward-curling leaf phenotype. Further investigation showed that the RNA level of IAA carboxyl methyltransferase 1 (IAMT1), encoding an enzyme involved in auxin metabolism, was dramatically elevated in the knockdown (SWI3B-RNAi) plants...
June 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29620420/research-progress-of-selective-small-molecule-bromodomain-containing-protein-9-inhibitors
#4
Ma Hui, Zhang Jian, Zheng Peiyuan, Wu Zhenwei, Zhang Huibin
The bromodomain proteins, known as the key targets in epigenetics, are 'readers' of acetylated lysine of histones. As a member of bromodomain proteins, bromodomain-containing protein 9 (BRD9) is a subunit of mammalian SWI/SNF chromatin remodeling complexes. However, the biological functions and the potential application in therapeutics of BRD9 remain ambiguous due to a lack of selective small molecule inhibitors of BRD9. Recently, series of chemical ligands against BRD9 were developed by different research institutes...
April 5, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29604291/arid1a-maintains-differentiation-of-pancreatic-ductal-cells-and-inhibits-development-of-pancreatic-ductal-adenocarcinoma-in-mice
#5
Yoshito Kimura, Akihisa Fukuda, Satoshi Ogawa, Takahisa Maruno, Yutaka Takada, Motoyuki Tsuda, Yukiko Hiramatsu, Osamu Araki, Munemasa Nagao, Takaaki Yoshikawa, Kozo Ikuta, Takuto Yoshioka, Zong Wang, Haruhiko Akiyama, Christopher V Wright, Kyoichi Takaori, Shinji Uemoto, Tsutomu Chiba, Hiroshi Seno
BACKGROUND & AIMS: The AT-rich interaction domain 1A gene (ARID1A) encodes a protein that is part of the large ATP-dependent chromatin remodeling complex SWI/SNF and is frequently mutated in human pancreatic ductal adenocarcinomas (PDACs). We investigated the functions of ARID1A during formation of PDACs in mice. METHODS: We performed studies with Ptf1a-Cre; KrasG12D mice, which express activated Kras in the pancreas and develop pancreatic intraepithelial neoplasias (PanINs), as well as those with disruption of Aird1a (Ptf1a-Cre; KrasG12D ; Arid1af/f mice) or disruption of Brg1 (encodes a catalytic ATPase of the SWI/SNF complex) (Ptf1a-Cre; KrasG12D ; Brg1f/f mice)...
March 28, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29596882/swi-snf-subunit-expression-heterogeneity-in-human-aplastic-anemia-stem-progenitors
#6
Sayantani Sinha, Shankha Subhra Chatterjee, Mayukh Biswas, Arijit Nag, Debasis Banerjee, Rajib De, Amitava Sengupta
Acquired aplastic anemia (AA) is a bone marrow failure that is associated with auto-immune destruction of hematopoietic stem cells (HSCs). Although somatic mutations have been identified in AA patients, mutations alone would not suffice understanding AA pathophysiology. SWI/SNF is an evolutionarily conserved, multi-subunit, ATP-dependent chromatin remodeling protein complex that plays important role in mammalian hematopoiesis. Herein, gene expression analysis identified a significant loss of SWI/SNF core component SMARCC1 along with ARID1B, ACTL6A and SMARCD1 in human AA bone marrow CD34+ HSC and progenitors (HSPCs) compared to normal HSPCs...
March 26, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29590609/repurposing-pan-hdac-inhibitors-for-arid1a-mutated-ovarian-cancer
#7
Takeshi Fukumoto, Pyoung Hwa Park, Shuai Wu, Nail Fatkhutdinov, Sergey Karakashev, Timothy Nacarelli, Andrew V Kossenkov, David W Speicher, Stephanie Jean, Lin Zhang, Tian-Li Wang, Ie-Ming Shih, Jose R Conejo-Garcia, Benjamin G Bitler, Rugang Zhang
ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2 in an ARID1A status-dependent manner...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29545370/pdgfr%C3%AE-translocates-to-the-nucleus-and-regulates-chromatin-remodeling-via-tata-element-modifying-factor-1
#8
Natalia Papadopoulos, Johan Lennartsson, Carl-Henrik Heldin
Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB-induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells...
March 15, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29535420/lncfzd6-initiates-wnt-%C3%AE-catenin-and-liver-tic-self-renewal-through-brg1-mediated-fzd6-transcriptional-activation
#9
Zhenzhen Chen, Yanfeng Gao, Lintong Yao, Yating Liu, Lan Huang, Zhongyi Yan, Wenshan Zhao, Pingping Zhu, Haibo Weng
Liver tumor-initiating cells (TICs), the drivers for liver tumorigenesis, accounts for liver tumor initiation, metastasis, drug resistance and relapse. Wnt/β-catenin signaling pathway emerges as a critical modulator in liver TIC self-renewal. However, the molecular mechanism of Wnt/β-catenin initiation in liver tumorigenesis and liver TICs is still elusive. Here, we examined the expression pattern of 10 Wnt receptors (FZD1-FZD10), and found only FZD6 is overexpressed along with liver tumorigenesis. What's more, a divergent lncRNA of FZD6, termed lncFZD6, is also highly expressed in liver cancer and liver TICs...
March 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29528755/emerging-therapeutic-targets-for-the-treatment-of-malignant-rhabdoid-tumors
#10
Karolina Nemes, Michael C Frühwald
Malignant Rhabdoid Tumor (MRT) is a rare and highly aggressive malignancy primarily affecting infants and young children. The most common anatomic locations are the central nervous system (AT/RT), the kidneys (RTK) and other soft tissues (eMRT). The genetic origin of this disease is linked to mutations in SMARCB1, a gene encoding a core subunit of the SWI/SNF chromatin-remodeling complex. Areas covered: Conventional multimodal treatment may offer a significant survival benefit to certain patients. It remains to be determined, however, which patients will prove resistant to chemotherapy and need novel therapeutic approaches...
March 12, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29523178/the-bromodomain-containing-protein-ibd1-links-multiple-chromatin-related-protein-complexes-to-highly-expressed-genes-in-tetrahymena-thermophila
#11
Alejandro Saettone, Jyoti Garg, Jean-Philippe Lambert, Syed Nabeel-Shah, Marcelo Ponce, Alyson Burtch, Cristina Thuppu Mudalige, Anne-Claude Gingras, Ronald E Pearlman, Jeffrey Fillingham
BACKGROUND: The chromatin remodelers of the SWI/SNF family are critical transcriptional regulators. Recognition of lysine acetylation through a bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes, this function is attributed to SNF2/Brg1. RESULTS: Using affinity purification coupled to mass spectrometry (AP-MS) we identified members of a SWI/SNF complex (SWI/SNFTt ) in Tetrahymena thermophila. SWI/SNFTt is composed of 11 proteins, Snf5Tt , Swi1Tt , Swi3Tt , Snf12Tt , Brg1Tt , two proteins with potential chromatin-interacting domains and four proteins without orthologs to SWI/SNF proteins in yeast or mammals...
March 9, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29515757/swi-snf-aberrations-sensitize-pancreatic-cancer-cells-to-dna-crosslinking-agents
#12
Jean Davidson, Zhewei Shen, Xue Gong, Jonathan R Pollack
While gemcitabine has been the mainstay therapy for advanced pancreatic cancer, newer combination regimens (e.g. FOLFIRINOX) have extended patient survival, though carry greater toxicity. Biomarkers are needed to better stratify patients for appropriate therapy. Previously, we reported that one-third of pancreatic cancers harbor deletions or deleterious mutations in key subunits of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. The SWI/SNF complex mobilizes nucleosomes on DNA, and plays a key role in modulating DNA transcription and repair...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29502955/the-ss18-ssx-oncoprotein-hijacks-kdm2b-prc1-1-to-drive-synovial-sarcoma
#13
Ana Banito, Xiang Li, Aimée N Laporte, Jae-Seok Roe, Francisco Sanchez-Vega, Chun-Hao Huang, Amanda R Dancsok, Katerina Hatzi, Chi-Chao Chen, Darjus F Tschaharganeh, Rohit Chandwani, Nilgun Tasdemir, Kevin B Jones, Mario R Capecchi, Christopher R Vakoc, Nikolaus Schultz, Marc Ladanyi, Torsten O Nielsen, Scott W Lowe
Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands...
February 22, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29483235/smarcb1-deficiency-integrates-epigenetic-signals-to-oncogenic-gene-expression-program-maintenance-in-human-acute-myeloid-leukemia
#14
Shankha Subhra Chatterjee, Mayukh Biswas, Liberalis Debraj Boila, Debasis Banerjee, Amitava Sengupta
SWI/SNF is an evolutionarily conserved multi-subunit chromatin remodeling complex that regulates epigenetic architecture and cellular identity. Although SWI/SNF genes are altered in ~ 25% of human malignancies, evidences showing their involvement in tumor cell-autonomous chromatin regulation and transcriptional plasticity are limiting. This study demonstrates that human primary acute myeloid leukemia (AML) cells exhibit near complete loss of SMARCB1 (BAF47 or SNF5/INI1) and SMARCD2 (BAF60B) associated with nucleation of SWI/SNFΔ...
February 26, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29482773/the-swi-snf-complex-subunit-genes-their-functions-variations-and-links-to-risk-and-survival-outcomes-in-human-cancers
#15
REVIEW
Sevtap Savas, Georgia Skardasi
SWI/SNF is a multiprotein complex essential for regulation of eukaryotic gene expression. In this article, we review the function and characteristics of this complex and its subunits in cancer-related phenotypes. We also present and discuss the publically available survival analysis data for TCGA patient cohorts, revealing novel relationships between the expression levels of the SWI/SNF subunit genes and patient survival times in several cancers. Overall, multiple lines of research point to a wide-spread role for the SWI/SNF complex genes in human cancer susceptibility and patient survival times...
March 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29482581/the-chromatin-remodeling-subunit-baf200-promotes-normal-hematopoiesis-and-inhibits-leukemogenesis
#16
Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
BACKGROUND: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis...
February 26, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29458976/small-cell-cancers-of-the-female-genital-tract-molecular-and-clinical-aspects
#17
REVIEW
Jay R Patibandla, Julia E Fehniger, Douglas A Levine, Petar Jelinic
OBJECTIVE: Extra-pulmonary small cell carcinomas of the gynecologic tract (EPSCC-GTs) are a rare group of aggressive malignancies associated with poor prognoses and limited treatment options. Here, we review the clinical and molecular aspects of EPSCC-GTs and discuss how understanding their molecular features can assist in their diagnosis and the identification of novel effective treatments. METHODS: We searched PubMed and Scopus for articles using the following keywords: "small cell carcinoma" in combination with "neuroendocrine", "ovary", "vagina", "fallopian tube", "vulva", "endometrium", "uterus", "cervix", or "gynecologic"...
February 17, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29434842/comprehensive-characterization-of-cancer-genes-in-hepatocellular-carcinoma-genomes
#18
Zhihao Zhang, Liping Xu, Changyu Sun
The present study was performed to detect moderate or low-frequency mutated cancer driver genes in hepatocellular carcinoma (HCC), using OncodriveFM and Dendrix. Following this, integrated analyses were conducted on these novel cancer driver genes. A total of 112,980 somatic mutations were retrieved from TCGA and classified into 11 categories based on their function. Driver genes and pathways were predicted by OncodriveFM and Dendrix, followed by differential expression, DNA-methylation, copy number variations and survival analyses...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29427621/brg1-promotes-liver-fibrosis-via-activation-of-hepatic-stellate-cells
#19
Haijie Li, Jingqin Lan, Caishun Han, Kaixuan Guo, Guihua Wang, Junbo Hu, Jianping Gong, Xuelai Luo, Zhixin Cao
Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by the persistent deposition of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Brg1, the core subunit of the SWI/SNF chromatin remodeling complex, has been proved to associated with nonalcoholic steatohepatitis which may progress to cirrhosis. Herein, we determined whether Brg1 regulates liver fibrosis and examined its mechanism by focusing on HSCs activation...
February 7, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29397238/hereditary-swi-snf-complex-deficiency-syndromes
#20
REVIEW
Abbas Agaimy, William D Foulkes
The SWItch Sucrose non-fermentable (SWI/SNF) complex is a highly conserved multi-subunit complex of proteins encoded by numerous genes mapped to different chromosomal regions. The complex regulates the process of chromatin remodelling and hence plays a central role in the epigenetic regulation of gene expression, cell proliferation and differentiation. During the last three decades, the SWI/SNF complex has been increasingly recognized as a central molecular event driving the initiation and/or progression of several benign and malignant neoplasms of different anatomic origin and having diverse histomorphological appearance...
February 1, 2018: Seminars in Diagnostic Pathology
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