Prostate Cell News Volume 9.18 | May 18 2018

TOP STORY

Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer

Treatment of castration-resistant prostate cancer (CRPC) cells with C86 or the allosteric heat shock protein 70 (Hsp70) inhibitor JG98 resulted in rapid protein destabilization of both full length-androgen receptor (FL-AR) and AR splice variants (ARv), including ARv7, concomitant with reduced FL-AR- and ARv7-mediated transcriptional activity. [Cancer Res] Abstract

(Ranked by impact factor of the journal)

An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer

Pygopus family PHD finger 2 (PYGO2) depletion inhibited prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo. In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impaired tumor progression. [Cancer Res] Abstract

COX-2 Mediates Pro-Tumorigenic Effects of PKCε in Prostate Cancer

Researchers showed that PKCε overexpression acted synergistically with Pten loss to promote NF-κB activation and induce cyclooxygenase-2 (COX-2) expression, phenotypic traits which are also observed in human prostate tumors. Targeted disruption of PKCε from prostate cancer cells impaired COX-2 induction and PGE2 production. [Oncogene] Abstract

Molecular Mechanism of the TP53-MDM2-AR-AKT Signaling Network Regulation by USP12

The authors found that USP12 deubiquitinated MDM2 and AR, which in turn controlled the levels of the TP53 tumor suppressor and AR oncogene in prostate cancer. [Oncogene] Abstract

Endothelial Akt1 Loss Promotes Prostate Cancer Metastasis via Β-Catenin-Regulated Tight-Junction Protein Turnover

Investigators showed that metastatic human PC3 and DU145 prostate cancer cells invade through Akt1-deficient human lung endothelial cell (HLEC) monolayer with higher efficiency compared to control HLEC. Although the endothelial Akt1 loss in mice had no significant effect on RM1 tumor xenograft growth in vivo, it promoted metastasis to the lungs compared to the wild-type mice. [Br J Cancer] Abstract

NDRG3 Lowers the Metastatic Potential in Prostate Cancer as a Feedback Controller of Hypoxia-Inducible Factors

Scientists investigated how N-myc downstream-regulated gene 3 (NDRG3) affects the hypoxic response in prostate cancer cells. Compared with hypoxia-inducible factors (HIF)-1α, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1α by inhibiting AKT-driven translation of HIF1A mRNA. NDRG3 functionally inhibited HIF-1 by dissociating the coactivator p300 from HIF-1α. [Exp Mol Med] Full Article

Novel Regulation of Integrin Trafficking by Rab11-FIP5 in Aggressive Prostate Cancer

Depletion of Rab11 family interacting protein 5 (Rab11-FIP5) resulted in the intracellular accumulation of α6β1 in the Rab11 recycling compartment, loss of cell migration on laminin, and an unexpected loss of α6β1 recycling in cell-cell locations. [Mol Cancer Res] Abstract

ZEB1-Mediated Vasculogenic Mimicry Formation Associates with Epithelial-Mesenchymal Transition and Cancer Stem Cell Phenotypes in Prostate Cancer

Zinc finger E‐box‐binding homeobox 1 (ZEB1) was required for VM formation and altered expression of epithelial-mesenchymal transition‐related and cancer stem cell‐associated proteins in prostate cancer cells in vitro and in vivo. ZEB1 also facilitated tumor cell migration, invasion and clonogenicity. [J Cell Mol Med] Full Article

Prevention of Prostate Cancer by Natural Product MDM2 Inhibitor GS25: In Vitro and In Vivo Activities and Molecular Mechanisms

The authors demonstrated that 25-OCH3-protopanaxadiol (GS25) inhibited prostate tumorigenesis and metastasis with minimal host toxicity. GS25 directly bound to the RING domain of MDM2, disrupted MDM2-MDMX binding, and induced MDM2 protein degradation, resulting in strong inhibition of prostate cancer cell growth and metastasis, independent of p53 and androgen receptor status. [Carcinogenesis] Abstract

Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) Is Upregulated during Prostate Cancer Progression and Modulates Cell Growth and Metastasis

Investigators showed that eIF4G1 expression was increased in prostate cancer (PCa) and that increased eIF4G1 expression associated with tumor progression and metastasis. They also observed high protein levels of eIF4G1 in PCa cell lines and prostate tissues from the TRAMP model of PCa as compared to normal prostate cell line and prostate tissues from wild type mice. [Sci Rep] Full Article

MicroRNAs as Potential Therapeutics to Enhance Chemosensitivity in Advanced Prostate Cancer

Scientists performed a genome-wide screen of 1280 microRNAs in the castration-resistant prostate cancer cell lines PC3 and DU145 in combination with docetaxel or cabazitaxel treatment. Mimics of miR-217 and miR-181b-5p enhanced apoptosis significantly in PC3 cells in the presence of these taxanes. [Sci Rep] Full Article

Translational Models of Prostate Cancer Bone Metastasis

An introspective appraisal of current preclinical models demonstrating bone metastases is warranted to narrow research focus, improve future translational modelling, and expedite the delivery of urgently needed metastasis-directed treatments. [Nat Rev Urol] Abstract

Systemic Treatments for High-Risk Localized Prostate Cancer

Combinations of neoadjuvant and adjuvant chemotherapy, hormonal therapy, or chemohormonal therapy are considered to be the standard of care in most solid tumors and should be investigated in the future for the treatment of prostate cancer to improve patient outcomes. The development of next-generation hormonal agents, which have been approved for the treatment of castration-resistant prostate cancer, offers further therapeutic possibilities that are being assessed in early-phase clinical trials. [Nat Rev Urol] Abstract

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

Janssen to Present New Data in Urothelial, Hematologic and Prostate Cancers

The Janssen Pharmaceutical Companies of Johnson & Johnson announced 21 company-sponsored abstracts will be presented. [Press release from Janssen Global Services, LLC discussing research to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Keck School of Medicine of USC Urologists to Present Latest Research

From robotics and machine learning to new applications for MRIs, Keck School of Medicine of USC scientists will present research highlighting the impact of technology on patient outcomes and the field of urology. [Press release from Keck School of Medicine (PR Newswire Association LLC.) discussing research to be presented at the American Urological Association 2018 annual meeting, San Francisco] Press Release

Bayer Highlights Latest Oncology Research

Clinical research to be presented from Bayer’s growing oncology portfolio, including radium-223 dichloride, sorafenib, regorafenib, copanlisib and other pipeline compounds. [Press release from Bayer AG discussing research to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Minomic Completes Prospective Clinical Study Using MiCheck^® to Assist in Diagnosis of Prostate Cancer

Minomic International Ltd, announced the completion of its prospective clinical trial of the company’s novel prostate cancer diagnostic test, MiCheck^®. The trial demonstrated utility identifying patients with elevated PSA who did not require a biopsy. The prospective trial demonstrated that using MiCheck^® could reduce the number of patients (with a clinically elevated PSA) proceeding to biopsy by up to 58%. [MINOMIC] Press Release

Dendreon Initiates Large-Scale Clinical Trial to Investigate PROVENGE^® (Sipuleucel-T) in Men with Early-Stage Prostate Cancer on Active Surveillance

Dendreon Pharmaceuticals LLC, announced it will conduct a large-scale, placebo-controlled clinical trial evaluating the effectiveness of PROVENGE^® in reducing disease progression in men with prostate cancer on active surveillance. PROVENGE was the first FDA-approved immunotherapy made from a patient’s own immune cells and remains the only immunotherapy treatment for prostate cancer. [Dendreon Pharmaceuticals LLC (Business Wire, Inc.)] Press Release

UK’s Powerful Funding Body Takes Shape

The United Kingdom’s newly minted unified funding agency has released the first outline of its strategy. The long-awaited document gives the nation’s researchers an insight into how the mega-funding agency — which will command a budget of £6 billion (US$8 billion) — will work. [Nature News] Editorial

Head of Controversial Agency Becomes Russian Minister for Science and Higher Education

In a major restructuring, the Russian government has decided to split its Ministry of Education and Science here into two new departments: the Ministry of Education, responsible for primary and secondary education, and a new, separate Ministry for Science and Higher Education. [ScienceInsider] Editorial

Europe’s Open-Access Drive Escalates As University Stand-Offs Spread

Bold efforts to push academic publishing towards an open-access model are gaining steam. Negotiators from libraries and university consortia across Europe are sharing tactics on how to broker new kinds of contracts that could see more articles appear outside paywalls. [Nature News] Editorial

Sacked Japanese Biologist Gets Chance to Retrain at Crick Institute

Prominent cell biologist Yoshinori Watanabe, who was dismissed by the University of Tokyo last month, is attempting to put his past behind him by embarking on an intensive retraining program with Nobel prizewinner Paul Nurse in London. The university dismissed Watanabe after an investigation concluded that he had committed scientific misconduct. [Nature News] Editorial

NEW 30^th EORTC-NCI-AACR Symposium
November 13-16, 2018
Dublin, Ireland

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

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

NEW 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)

Tenure-Track Faculty Position – Cancer Research (University of Ottawa)

Postdoctoral Fellow – Prostate Cancer (Moffitt Cancer Center)

Postdoctoral Fellow – Prostate Cancer Epigenomics (Northwestern University)

Postdoctoral Fellows – Molecular and Translational Cancer Biology (Thomas Jefferson University)

Postdoctoral Position – Prostate Cancer (Northwestern University)

Postdoctoral Associate – Prostate Research (Baylor College of Medicine)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Prostate Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.