Prostate Cell News Volume 9.20 | June 1 2018

TOP STORY

Analysis of the Androgen Receptor–Regulated lncRNA Landscape Identifies a Role for ARLNC1 in Prostate Cancer Progression

Researchers identified androgen receptor (AR)-regulated long noncoding RNA 1 (ARLNC1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA–RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. [Nat Genet] Abstract | Press Release

(Ranked by impact factor of the journal)

Diverse AR-V7 Cistromes in Castration-Resistant Prostate Cancer Are Governed by HoxB13

Investigators showed androgen receptor splice variant 7 (AR-V7) bound to distinct genomic regions and recognized a full-length androgen-responsive element in castration-resistant prostate cancer (CRPC) cells and patient tissues. They discover that HoxB13 was universally required for and colocalized with AR-V7 binding to open chromatin across CRPC genomes. [Proc Natl Acad Sci USA] Abstract

TMPRSS2-ERG Controls Luminal Epithelial Lineage and Antiandrogen Sensitivity in PTEN and TP53-Mutated Prostate Cancer

Transgenic ERG expression in mice blocked Pten/Trp53 alteration-induced decrease of AR expression and downstream luminal epithelial genes. ERG directly suppressed expression of cell cycle-related genes, which induced RB hypophosphorylation and repressed E2F1-mediated expression of mesenchymal lineage regulators, thereby restricting adenocarcinoma plasticity and maintaining antiandrogen sensitivity. [Clin Cancer Res] Abstract

The p21-Activated Kinase 4-Slug Transcription Factor Axis Promotes Epithelial-Mesenchymal Transition and Worsens Prognosis in Prostate Cancer

Scientists found that phosphorylated p21-activated kinase 4 (PAK4^S474) levels, an index of PAK4 activation, were tightly associated with Gleason score, a clinical indicator of prostate cancer (PC) progression, but not with prostate serum antigen levels or tumor stage. Stable silencing of PAK4 in PC cells reduced their potential for epithelial-mesenchymal transition, cellular invasion, and metastasis in vivo. [Oncogene] Abstract

Loss of MAOA in Epithelia Inhibits Adenocarcinoma Development, Cell Proliferation and Cancer Stem Cells in Prostate

Researchers investigated the role of monoamine oxidase A (MAOA) in the development of prostate adenocarcinoma by creating a prostate-specific Pten/MAOA knockout (KO) mouse model, in which MAOA-floxP mouse was crossed with the conditional Pten KO prostate cancer (PCa) mouse that develops invasive PCa. [Oncogene] Abstract

A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor

The authors characterized the effects of receptor activation on metabolism using a prostate cancer cell line and demonstrated decreased intracellular anabolic signals and cell viability, induction of cell cycle arrest, and increased expression of neuronal markers. Upregulation of neuron-specific enolase by agonist treatment was abolished in OR51E2-KO cells. [Front Oncol] Full Article | Press Release

MiRNA-106a and Prostate Cancer Radioresistance: A Novel Role for LITAF in ATM Regulation

Scientists identified that miR-106a was overexpressed in radiation-resistant cells compared to parental cells. In the Cancer Genome Atlas, miR‐106a was significantly elevated in high-grade human prostate tumors relative to intermediate- and low-grade specimens. MiR-106a overexpression conferred radioresistance by increasing proliferation and reducing senescence, and this was phenocopied by knockdown of lipopolysaccharide-induced TNF- α factor (LITAF). [Mol Oncol] Abstract | Full Article

CRISPR-Mediated Reactivation of DKK3 Expression Attenuates TGF-β Signaling in Prostate Cancer

Investigators showed that treatment of PC3 prostate cancer cells with the DNA methyltransferase inhibitor decitabine demethylated the DKK3 promoter, induced DKK3 expression, and inhibited TGF-β/Smad-dependent transcriptional activity. Direct induction of DKK3 expression using CRISPR-dCas9-VPR inhibited TGF-β/Smad-dependent transcription and attenuated PC3 cell migration and proliferation. [Cancers] Full Article

Prostate Derived Ets Factor (PDEF) Inhibits Metastasis by Inducing Epithelial/Luminal Phenotype in Prostate Cancer Cells

Twist1 knockdown resulted in upregulation of PDEF expression, suggesting a reciprocal regulation between PDEF and Twist1. PDEF directly regulated cytokeratin 18 (CK18) transcription through the GGAT motif within its putative promoter region. CK18 knockdown resulted in increased expression of Twist1, suggesting that PDEF regulated Twist1 in part via CK18. [Mol Cancer Res] Abstract

High-Throughput Screening Identified Selective Inhibitors of Exosome Biogenesis and Secretion: A Drug Repurposing Strategy for Advanced Cancer

Twenty-two compounds were found to be either potent activators or inhibitors of intracellular GFP signal in the CD63-GFP-expressing C4-2B cells. The lead compounds tipifarnib, neticonazole, climbazole, ketoconazole, and triademenol were validated as potent inhibitors and sitafloxacin, forskolin, SB218795, fenoterol, nitrefazole and pentetrazol as activators of exosome biogenesis and/or secretion in prostate cancer cells. [Sci Rep] Full Article

AR Signaling in Prostate Cancer Regulates a Feed-Forward Mechanism of Androgen Synthesis by Way of HSD3B1 Upregulation

Researchers found that VCaP, CWR22Rv1, LNCaP, and LAPC4 models demonstrated induction of HSD3B1 upon androgen stimulation for approximately 72 hours followed by attenuation around 120 hours. HSD3B1 expression was reduced 72 hours post-castration in the VCaP xenograft mouse model, suggesting AR regulation of HSD3B1 also occurs in vivo. [Endocrinology] Abstract

Prostate Cancer Stem Cells: Current Understanding

The authors discuss the current methods for prostate cancer stem cell (PCSC) enrichment and analysis, the hallmarks of PCSC metabolism and the role of PCSCs in tumor progression. [Stem Cells] Abstract | Full Article

Visit our reviews page to see a complete list of reviews in the prostate cell research field.

PROCEPT BioRobotics’ Aquablation Meets Primary Endpoints in WATER II Study of 80 to 150 Milliliter Prostates

PROCEPT BioRobotics, has announced early data from the global Phase III WATER II (Waterjet Ablation Therapy for Endoscopic Resection of prostate tissue) Study showing the achievement of primary safety and efficacy endpoints for Aquablation in the treatment of benign prostatic hyperplasia. [Press release from PROCEPT BioRobotics, Inc. discussing research presented at the American Urological Association (AUA) Annual Meeting, San Francisco] Press Release

Bayer and MD Anderson Cancer Center to Collaborate on Development of Novel Cancer Treatments

Bayer and the University of Texas MD Anderson Cancer Center have signed a five-year collaboration agreement to accelerate the development of novel targeted treatments based on patient or tumor characteristics for which current therapies have not shown satisfactory clinical efficacy. [Bayer AG] Press Release

UT Health San Antonio Receives $24 Million NIH Research Boost

For the third time in ten years, UT Health San Antonio has garnered highly competitive National Institutes of Health (NIH) grants to speed the translation of research discovery into improved patient care. UT Health San Antonio will receive $24 million over the next five years under the Clinical and Translational Science Award Program. [UT Health San Antonio] Press Release

ORNL Ramps Up Production of Key Radioisotope for Cancer-Fighting Drug

The Department of Energy’s Oak Ridge National Laboratory (ORNL) is now producing actinium-227 (Ac-227) to meet projected demand for a highly effective cancer drug through a ten-year contract between the U.S. DOE Isotope Program and Bayer. Xofigo is used to treat prostate cancer that no longer responds to hormonal or surgical treatment that lowers testosterone. Ra-223, the active ingredient in Xofigo, is currently derived from global supplies of existing Ac-227. [Oak Ridge National Laboratory] Press Release

Who Gets Credit for CRISPR? Prestigious Award Singles Out Three, and Leaves Out a Notable Scientist

One of the world’s richest science awards, given only in alternate years, will go to three discoverers of the CRISPR-Cas9 genome-editing tool, the Norwegian Academy of Science and Letters announced. Emmanuelle Charpentier of the Max Planck Institute for Infection Biology, Jennifer Doudna of the University of California, Berkeley, and Virginijus Šikšnys of Vilnius University will each receive a gold medal and share the $1 million that comes with the Kavli Prize in nanoscience. [STAT News] Editorial

Europe’s Science Spending Set for Another Big Boost

On 7 June, the European Commission will lay out detailed plans for one of the biggest single research programs on the planet. Called Horizon Europe, the program could be worth €97.6 billion between 2021 and 2027, up from about €77 billion for the current seven-year program, Horizon 2020. Its influence, however, will go beyond size. [ScienceInsider] Editorial

Max Planck Scientists Criticize Handling of Animal-Rights Charges against Leading Neuroscientist

Scientists at one of Germany’s leading neuroscience institutes say that their employer, the Max Planck Society, is failing in its responsibility to defend the institute’s scientists against efforts by animal-rights activists to disrupt research. [Nature News] Editorial

After Brexit, Can British Science Have Its Cake and Eat It, Too?

Nearly two years after Britons voted to leave the European Union, Brexit’s impact on European science is finally coming into focus. Prime Minister Theresa May announced that the United Kingdom wants to take part in the next EU research-funding program, set to be worth almost €100 billion (US$116 billion). [Nature News] Editorial

Sweden Commits to Open Science with New Open-Access Publishing Deal

Swedish researchers can now publish their articles in Frontiers’ Open Access journals through a simplified process that covers publishing fees, thanks to a national agreement announced between Frontiers and the National Library of Sweden, on behalf of the organizations participating in the Bibsam Consortium. [EurekAlert] Editorial

China to Crack Down on Fraud in Scandal-Hit Scientific Research amid ZTE Wrangle

China has issued the first national guidelines to enforce academic integrity in scientific research and vowed to punish academics and institutes for misconduct such as plagiarism and fabrication of data. [South China Morning Post Publishers Ltd.] Editorial

NEW The New York Stem Cell Foundation (NYSCF) Conference
October 23-24, 2018
New York, New York, United States

Visit our events page to see a complete list of events in the community.

NEW Research Fellow – Prostate Cancer (Sechenov University)

Postdoctoral Position – Steroid Hormone Production and Signaling (University of Rochester Medical Center)

Postdoctoral Positions – Transcriptional/Epigenetic Regulation in Cancer Progression (UT Health San Antonio)

Postdoctoral Fellow/Research Scientists – Prostate Cancer Research (Institute of Oncology Research – Universita della Svizzera Italiana)

Postdoctoral Position – Drug Discovery for Advance Prostate Cancer (Lerner Research Institute – Cleveland Clinic)

Postdoctoral Fellow – Computational Genomics of Cancer (Cold Spring Harbor Laboratory)

Research Associate – Computational Biology (University College London)

Academic Position – Cancer Research (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Prostate Cancer (Moffitt Cancer Center)

Postdoctoral Associate – Prostate Research (Baylor College of Medicine)

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