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https://www.readbyqxmd.com/read/27898096/on-a-fox-hunt-functions-of-fox-transcriptional-regulators-in-bladder-cancer
#1
REVIEW
Hironobu Yamashita, Vasty Osei Amponsa, Joshua I Warrick, Zongyu Zheng, Peter E Clark, Jay D Raman, Xue-Ru Wu, Cathy Mendelsohn, David J DeGraff
Genomic and transcriptional studies have identified discrete molecular subtypes of bladder cancer. These observations could be the starting point to identify new treatments. Several members of the forkhead box (FOX) superfamily of transcription factors have been found to be differentially expressed in the different bladder cancer subtypes. In addition, the FOXA protein family are key regulators of embryonic bladder development and patterning. Both experimental and clinical data support a role for FOXA1 and FOXA2 in urothelial carcinoma...
November 29, 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27883218/tyrosine-phosphorylation-of-the-pioneer-transcription-factor-foxa1-promotes-activation-of-estrogen-signaling
#2
Noritaka Yamaguchi, Misato Shibazaki, Chiaki Yamada, Erina Anzai, Mariko Morii, Yuji Nakayama, Takahisa Kuga, Yuuki Hashimoto, Takeshi Tomonaga, Naoto Yamaguchi
The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA. In this study, we analyzed tyrosine phosphorylation of FoxA1 by the non-receptor-type tyrosine kinase c-Abl. c-Abl was shown to phosphorylate FoxA1 at multiple sites, especially in the N- and C-terminal regions. Tyr429 and Tyr464 were identified as the major phosphorylation sites in the FoxA1 C-terminal region. The phosphomimetic and nonphosphorylatable FoxA1 mutants were generated by glutamic acid and phenylalanine substitutions at these tyrosine residues, respectively...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27867534/nanog-reprograms-prostate-cancer-cells-to-castration-resistance-via-dynamically-repressing-and-engaging-the-ar-foxa1-signaling-axis
#3
Collene R Jeter, Bigang Liu, Yue Lu, Hsueh-Ping Chao, Dingxiao Zhang, Xin Liu, Xin Chen, Qiuhui Li, Kiera Rycaj, Tammy Calhoun-Davis, Li Yan, Qiang Hu, Jianmin Wang, Jianjun Shen, Song Liu, Dean G Tang
The pluripotency transcription factor NANOG has been implicated in tumor development, and NANOG-expressing cancer cells manifest stem cell properties that sustain tumor homeostasis, mediate therapy resistance and fuel tumor progression. However, how NANOG converges on somatic circuitry to trigger oncogenic reprogramming remains obscure. We previously reported that inducible NANOG expression propels the emergence of aggressive castration-resistant prostate cancer phenotypes. Here we first show that endogenous NANOG is required for the growth of castration-resistant prostate cancer xenografts...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27835577/a-functional-variant-rs4442975-modulating-foxa1-binding-affinity-does-not-influence-the-risk-or-progression-of-breast-cancer-in-chinese-han-population
#4
Yi Zhang, Yan Li, Shaojie Jiang, Wei Chen, Jiao Lou, Juntao Ke, Jiaoyuan Li, Ying Zhu, Yajie Gong, Yang Yang, Jianbo Tian, Xiating Peng, Danyi Zou, Jing Gong, Jiang Chang, Xiaoping Miao, Rong Zhong
The DNA-binding protein FOXA1 has been shown to regulate nearly all estrogen receptor-chromatin interactions, thereby influencing target gene expression levels in breast cancer (BC) cells. Recently, the rs4442975 T-allele, which disrupts the recruitment of FOXA1 and interacts with the IGFBP5 promoter, was associated to BC susceptibility in a European population. We conducted a hospital-based case-control study that included 1227 cases and 1285 controls to explore the potential association between rs4442975 and BC risk in Chinese Han population, and the effect of this SNP on BC progression was also observed in cases...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27829043/microrna-93-promotes-epithelial-mesenchymal-transition-of-endometrial-carcinoma-cells
#5
Shuo Chen, Xi Chen, Kai-Xuan Sun, Yin-Ling Xiu, Bo-Liang Liu, Miao-Xiao Feng, Xiu-Bo Sang, Yang Zhao
MicroRNA-93, derived from a paralog (miR-106b-25) of the miR-17-92 cluster, is involved in the tumorigenesis and progression of many cancers such as breast, colorectal, hepatocellular, lung, ovarian, and pancreatic cancer. However, the role of miR-93 in endometrial carcinoma and the potential molecular mechanisms involved remain unknown. Our results showed that miR-93 was overexpressed in endometrial carcinoma tissues than normal endometrial tissues. The endometrial carcinoma cell lines HEC-1B and Ishikawa were transfected with miR-93-5P, after which cell migration and invasion ability and the expression of relevant molecules were detected...
2016: PloS One
https://www.readbyqxmd.com/read/27811935/integrated-computational-approach-to-the-analysis-of-rna-seq-data-reveals-new-transcriptional-regulators-of-psoriasis
#6
Alena Zolotarenko, Evgeny Chekalin, Alexandre Mesentsev, Ludmila Kiseleva, Elena Gribanova, Rohini Mehta, Ancha Baranova, Tatiana V Tatarinova, Eleonora S Piruzian, Sergey Bruskin
Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements...
November 4, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27807832/transcriptome-and-proteome-analyses-of-tnfaip8-knockdown-cancer-cells-reveal-new-insights-into-molecular-determinants-of-cell-survival-and-tumor-progression
#7
Timothy F Day, Rajshree R Mewani, Joshua Starr, Xin Li, Debyani Chakravarty, Habtom Ressom, Xiaojun Zou, Ofer Eidelman, Harvey B Pollard, Meera Srivastava, Usha N Kasid
Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is the first discovered oncogenic and an anti-apoptotic member of a conserved TNFAIP8 or TIPE family of proteins. TNFAIP8 mRNA is induced by NF-kB, and overexpression of TNFAIP8 has been correlated with poor prognosis in many cancers. Downregulation of TNFAIP8 expression has been associated with decreased pulmonary colonization of human tumor cells, and enhanced sensitivities of tumor xenografts to radiation and docetaxel. Here we have investigated the effects of depletion of TNFAIP8 on the mRNA, microRNA and protein expression profiles in prostate and breast cancers and melanoma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27802415/genome-wide-and-gene-based-meta-analyses-identify-novel-loci-influencing-blood-pressure-response-to-hydrochlorothiazide
#8
Erika Salvi, Zhiying Wang, Federica Rizzi, Yan Gong, Caitrin W McDonough, Sandosh Padmanabhan, Timo P Hiltunen, Chiara Lanzani, Roberta Zaninello, Martina Chittani, Kent R Bailey, Antti-Pekka Sarin, Matteo Barcella, Olle Melander, Arlene B Chapman, Paolo Manunta, Kimmo K Kontula, Nicola Glorioso, Daniele Cusi, Anna F Dominiczak, Julie A Johnson, Cristina Barlassina, Eric Boerwinkle, Rhonda M Cooper-DeHoff, Stephen T Turner
This study aimed to identify novel loci influencing the antihypertensive response to hydrochlorothiazide monotherapy. A genome-wide meta-analysis of blood pressure (BP) response to hydrochlorothiazide was performed in 1739 white hypertensives from 6 clinical trials within the International Consortium for Antihypertensive Pharmacogenomics Studies, making it the largest study to date of its kind. No signals reached genome-wide significance (P<5×10(-)(8)), and the suggestive regions (P<10(-5)) were cross-validated in 2 black cohorts treated with hydrochlorothiazide...
October 31, 2016: Hypertension
https://www.readbyqxmd.com/read/27791031/foxa1-overexpression-mediates-endocrine-resistance-by-altering-the-er-transcriptome-and-il-8-expression-in-er-positive-breast-cancer
#9
Xiaoyong Fu, Rinath Jeselsohn, Resel Pereira, Emporia F Hollingsworth, Chad J Creighton, Fugen Li, Martin Shea, Agostina Nardone, Carmine De Angelis, Laura M Heiser, Pavana Anur, Nicholas Wang, Catherine S Grasso, Paul T Spellman, Obi L Griffith, Anna Tsimelzon, Carolina Gutierrez, Shixia Huang, Dean P Edwards, Meghana V Trivedi, Mothaffar F Rimawi, Dolores Lopez-Terrada, Susan G Hilsenbeck, Joe W Gray, Myles Brown, C Kent Osborne, Rachel Schiff
Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor α (ER)-chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown. Here, we report preclinical evidence for a role of FOXA1 in Endo-R breast cancer as well as evidence for its clinical significance. FOXA1 is gene-amplified and/or overexpressed in Endo-R derivatives of several breast cancer cell line models. Induced FOXA1 triggers oncogenic gene signatures and proteomic profiles highly associated with endocrine resistance...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27787633/foxa1-gene-and-protein-in-developing-rat-eccrine-sweat-glands
#10
Haihong Li, Liyun Chen, Mingjun Zhang, Bingna Zhang
To investigate the development of eccrine sweat glands and the expression of Foxa1 genes and proteins in the course of development, the footpads from E15.5 to E21.5, P1-P12, P14, P21, P28 and P56 rats were subjected to immunofluorescence staining of FoxA1 and double immunofluorescence staining of K14/α-SMA, FoxA1/K7 and FoxA1/α-SMA, and were processed for Foxa1 gene detection by RT-qPCR. The results showed that rat eccrine sweat gland germs was first observed emerging from the basal layer of epidermis at E19...
October 27, 2016: Journal of Molecular Histology
https://www.readbyqxmd.com/read/27749322/clinical-validity-of-detecting-circulating-tumor-cells-by-adnatest-assay-compared-with-direct-detection-of-tumor-mrna-in-stabilized-whole-blood-as-a-biomarker-predicting-overall-survival-for-metastatic-castration-resistant-prostate-cancer-patients
#11
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
https://www.readbyqxmd.com/read/27739523/foxa-and-master-transcription-factors-recruit-mediator-and-cohesin-to-the-core-transcriptional-regulatory-circuitry-of-cancer-cells
#12
Michèle Fournier, Gaëlle Bourriquen, Fabien C Lamaze, Maxime C Côté, Éric Fournier, Charles Joly-Beauparlant, Vicky Caron, Stéphane Gobeil, Arnaud Droit, Steve Bilodeau
Controlling the transcriptional program is essential to maintain the identity and the biological functions of a cell. The Mediator and Cohesin complexes have been established as central cofactors controlling the transcriptional program in normal cells. However, the distribution, recruitment and importance of these complexes in cancer cells have not been fully investigated. Here we show that FOXA and master transcription factors are part of the core transcriptional regulatory circuitry of cancer cells and are essential to recruit M ediator and Cohesin...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721404/a-pre-neoplastic-epigenetic-field-defect-in-hcv-infected-liver-at-transcription-factor-binding-sites-and-polycomb-targets
#13
N A Wijetunga, M Pascual, J Tozour, F Delahaye, M Alani, M Adeyeye, A W Wolkoff, A Verma, J M Greally
The predisposition of patients with Hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) involves components of viral infection, inflammation and time. The development of multifocal, genetically distinct tumours is suggestive of a field defect affecting the entire liver. The molecular susceptibility mediating such a field defect is not understood. One potential mediator of long-term cellular reprogramming is heritable (epigenetic) regulation of transcription, exemplified by DNA methylation. We studied epigenetic and transcriptional changes in HCV-infected livers in comparison with control, uninfected livers and HCC, allowing us to identify pre-neoplastic epigenetic and transcriptional events...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27672107/somatic-mutation-copy-number-and-transcriptomic-profiles-of-primary-and-matched-metastatic-estrogen-receptor-positive-breast-cancers
#14
D Fumagalli, T R Wilson, R Salgado, X Lu, J Yu, C O'Brien, K Walter, L Y Huw, C Criscitiello, I Laios, V Jose, D N Brown, F Rothé, M Maetens, D Zardavas, P Savas, D Larsimont, M J Piccart-Gebhart, S Michiels, M R Lackner, C Sotiriou, S Loi
BACKGROUND: Estrogen receptor-positive (ER+) breast cancers (BCs) constitute the most frequent BC subtype. The molecular landscape of ER+ relapsed disease is not well characterized. In this study, we aimed to describe the genomic evolution between primary (P) and matched metastatic (M) ER+ BCs after failure of adjuvant therapy. MATERIALS AND METHODS: A total of 182 ER+ metastatic BC patients with long-term follow-up were identified from a single institution. P tumor tissue was available for all patients, with 88 having matched M material...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27672034/crosstalk-between-androgen-and-pro-inflammatory-signaling-remodels-androgen-receptor-and-nf-%C3%AE%C2%BAb-cistrome-to-reprogram-the-prostate-cancer-cell-transcriptome
#15
Marjo Malinen, Einari A Niskanen, Minna U Kaikkonen, Jorma J Palvimo
Inflammatory processes and androgen signaling are critical for the growth of prostate cancer (PC), the most common cancer among males in Western countries. To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, we have interrogated the crosstalk between androgen receptor (AR) and NF-κB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in PC cells...
September 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27634452/cell-lineage-specificity-and-role-of-ap-1-in-the-prostate-fibroblast-androgen-receptor-cistrome
#16
Damien A Leach, Vasilios Panagopoulos, Claire Nash, Charlotte Bevan, Axel A Thomson, Luke A Selth, Grant Buchanan
Androgen receptor (AR) signalling in fibroblasts is important in prostate development and carcinogenesis, and is inversely related to prostate cancer mortality. However, the molecular mechanisms of AR action in fibroblasts and other non-epithelial cell types are largely unknown. The genome-wide DNA binding profile of AR in human prostate fibroblasts was identified by chromatin immunoprecipitation sequencing (ChIP-Seq), and found to be common to other fibroblast lines but disparate from AR cistromes of prostate cancer cells and tissue...
September 12, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27633730/pioneer-factors-and-atp-dependent-chromatin-remodeling-factors-interact-dynamically-a-new-perspective-multiple-transcription-factors-can-effect-chromatin-pioneer-functions-through-dynamic-interactions-with-atp-dependent-chromatin-remodeling-factors
#17
Erin E Swinstead, Ville Paakinaho, Diego M Presman, Gordon L Hager
Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co-activators, co-repressors, multiple TFs, histone-modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering role...
September 16, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27625068/characterization-of-human-mitochondrial-ferritin-promoter-identification-of-transcription-factors-and-evidences-of-epigenetic-control
#18
Michela Guaraldo, Paolo Santambrogio, Elisabetta Rovelli, Augusta Di Savino, Giuseppe Saglio, Davide Cittaro, Antonella Roetto, Sonia Levi
Mitochondrial ferritin (FtMt) is an iron storage protein belonging to the ferritin family but, unlike the cytosolic ferritin, it has an iron-unrelated restricted tissue expression. FtMt appears to be preferentially expressed in cell types characterized by high metabolic activity and oxygen consumption, suggesting a role in protecting mitochondria from iron-dependent oxidative damage. The human gene (FTMT) is intronless and its promoter region has not been described yet. To analyze the regulatory mechanisms controlling FTMT expression, we characterized the 5' flanking region upstream the transcriptional starting site of FTMT by in silico enquiry of sequences conservation, DNA deletion analysis, and ChIP assay...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27601596/whole-genomic-copy-number-alterations-in-circulating-tumor-cells-from-men-with-abiraterone-or-enzalutamide-resistant-metastatic-castration-resistant-prostate-cancer
#19
Santosh Gupta, Jing Li, Gabor Kemeny, Rhonda L Bitting, Joshua Beaver, Jason Somarelli, Kathryn E Ware, Simon Gregory, Andrew J Armstrong
PURPOSE: Beyond enumeration, circulating tumor cells (CTCs) can provide genetic information from metastatic cancer that may facilitate a greater understanding of tumor biology and enable a precision medicine approach. EXPERIMENTAL DESIGN: CTCs and paired leukocytes from men with metastatic castration-resistant prostate cancer (mCRPC) were isolated from blood through red cell lysis, CD45 depletion, and flow sorting based on EpCAM/CD45 expression. We next performed whole genomic copy number analysis of CTCs and matched patient leukocytes (germline) using array-based comparative genomic hybridization (aCGH) from 16 men with mCRPC, including longitudinal and sequential CTCs aCGH analyses in the context of enzalutamide therapy...
September 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27524420/twist1-promotes-breast-cancer-invasion-and-metastasis-by-silencing-foxa1-expression
#20
Y Xu, L Qin, T Sun, H Wu, T He, Z Yang, Q Mo, L Liao, J Xu
The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis. However, the regulatory and functional relationships between Twist1 and Foxa1 in breast cancer progression are unknown...
August 15, 2016: Oncogene
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