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https://www.readbyqxmd.com/read/28038451/androgen-receptor-transcriptionally-regulates-semaphorin-3c-in-a-gata2-dependent-manner
#1
Kevin J Tam, Kush Dalal, Michael Hsing, Chi Wing Cheng, Shahram Khosravi, Parvin Yenki, Charan Tse, James W Peacock, Aishwariya Sharma, Yan Ting Chiang, Yuzhuo Wang, Artem Cherkasov, Paul S Rennie, Martin E Gleave, Christopher J Ong
The androgen receptor (AR) is a member of the nuclear receptor superfamily of transcription factors and is central to prostate cancer (PCa) progression. Ligand-activated AR engages androgen response elements (AREs) at androgen-responsive genes to drive the expression of gene batteries involved in cell proliferation and cell fate. Understanding the transcriptional targets of the AR has become critical in apprehending the mechanisms driving treatment-resistant stages of PCa. Although AR transcription regulation has been extensively studied, the signaling networks downstream of AR are incompletely described...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27997592/identification-of-post-transcriptional-modulators-of-breast-cancer-transcription-factor-activity-using-mindy
#2
Thomas M Campbell, Mauro A A Castro, Bruce A J Ponder, Kerstin B Meyer
We have recently identified transcription factors (TFs) that are key drivers of breast cancer risk. To better understand the pathways or sub-networks in which these TFs mediate their function we sought to identify upstream modulators of their activity. We applied the MINDy (Modulator Inference by Network Dynamics) algorithm to four TFs (ESR1, FOXA1, GATA3 and SPDEF) that are key drivers of estrogen receptor-positive (ER+) breast cancer risk, as well as cancer progression. Our computational analysis identified over 500 potential modulators...
2016: PloS One
https://www.readbyqxmd.com/read/27974698/genome-wide-copy-number-analyses-of-superficial-esophageal-squamous-cell-carcinoma-with-and-without-metastasis
#3
Pengjiao Wang, Ling Shan, Liyan Xue, Bo Zheng, Jianming Ying, Ning Lu
Superficial esophageal squamous cell carcinoma (ESCC) is generally considered a subtype of less invasive ESCC. Yet a subset of these superficial ESCC would have metastasis after esophagostomy or endoscopic resection and lead to poor prognosis. The objective of this study is to determine biomarkers that can identify such subset of superficial ESCC that would have metastasis after surgery using genome wide copy number alteration (CNA) analyses. The CNAs of 38 cases of superficial ESCCs originated from radical surgery, including 19 without metastasis and 19 with metastasis within 5 years' post-surgery, were analyzed using Affymetrix OncoScan™ FFPE Assay...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27959926/predictors-of-chemosensitivity-in-triple-negative-breast-cancer-an-integrated-genomic-analysis
#4
Tingting Jiang, Weiwei Shi, Vikram B Wali, Lőrinc S Pongor, Charles Li, Rosanna Lau, Balázs Győrffy, Richard P Lifton, William F Symmans, Lajos Pusztai, Christos Hatzis
BACKGROUND: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients. METHODS AND FINDINGS: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27934886/foxa1-is-essential-for-development-and-functional-integrity-of-the-subthalamic-nucleus
#5
Emanuel Gasser, Helge C Johannssen, Thomas Rülicke, Hanns Ulrich Zeilhofer, Markus Stoffel
Inactivation of transcription factor Foxa1 in mice results in neonatal mortality of unknown cause. Here, we report that ablation of Foxa1 causes impaired development and loss of the subthalamic nucleus (STN). Functional deficits in the STN have been implicated in the etiology of Huntington's and Parkinson's disease. We show that neuronal ablation by Synapsin1-Cre-mediated Foxa1 deletion is sufficient to induce hyperlocomotion in mice. Transcriptome profiling of STN neurons in conditional Foxa1 knockout mice revealed changes in gene expression reminiscent of those in neurodegenerative diseases...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27926873/foxa1-directs-h3k4-monomethylation-at-enhancers-via-recruitment-of-the-methyltransferase-mll3
#6
Kamila M Jozwik, Igor Chernukhin, Aurelien A Serandour, Sankari Nagarajan, Jason S Carroll
FOXA1 is a pioneer factor that binds to enhancer regions that are enriched in H3K4 mono- and dimethylation (H3K4me1 and H3K4me2). We performed a FOXA1 rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells and found histone-lysine N-methyltransferase (MLL3) as the top FOXA1-interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition. We performed MLL3 chromatin immunoprecipitation sequencing (ChIP-seq) in breast cancer cells, and MLL3 was shown to occupy regions marked by FOXA1 occupancy and H3K4me1 and H3K4me2...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#7
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers, and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), and are HER2-negative and of luminal 'intrinsic' subtype. Here, we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER(+) /HER2(-) ) breast carcinoma show distinct repertoires of somatic mutations. Eighteen ER(+) /HER2(-) NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissues were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast carcinomas and/or related to DNA repair...
December 7, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27924948/foxa1-gata3-and-ppar%C3%A9-cooperate-to-drive-luminal-subtype-in-bladder-cancer-a-molecular-analysis-of-established-human-cell-lines
#8
Joshua I Warrick, Vonn Walter, Hironobu Yamashita, Eunah Chung, Lauren Shuman, Vasty Osei Amponsa, Zongyu Zheng, Wilson Chan, Tiffany L Whitcomb, Feng Yue, Tejaswi Iyyanki, Yuka I Kawasawa, Matthew Kaag, Wansong Guo, Jay D Raman, Joo-Seop Park, David J DeGraff
Discrete bladder cancer molecular subtypes exhibit differential clinical aggressiveness and therapeutic response, which may have significant implications for identifying novel treatments for this common malignancy. However, research is hindered by the lack of suitable models to study each subtype. To address this limitation, we classified bladder cancer cell lines into molecular subtypes using publically available data in the Cancer Cell Line Encyclopedia (CCLE), guided by genomic characterization of bladder cancer by The Cancer Genome Atlas (TCGA)...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27898096/on-a-fox-hunt-functions-of-fox-transcriptional-regulators-in-bladder-cancer
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
January 2017: 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
#17
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
#18
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
#19
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
#20
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
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