Prostate Cell News Volume 8.10 | Mar 17 2017

TOP STORY

SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling

Scientists describe a mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions with striking nuclear atypia and invasive, poorly differentiated carcinoma. [Cancer Cell] Abstract | Graphical Abstract

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LABORATORY RESEARCH

MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions

The authors report that monoamine oxidase A (MAOA) is a clinically and functionally important mediator of prostate cancer bone and visceral metastases, activating paracrine Shh signaling in tumor-stromal interactions. MAOA provided tumor cell growth advantages in the bone microenvironment by stimulating interleukin-6 (IL6) release from osteoblasts, and triggered skeletal colonization by activating osteoclastogenesis through osteoblast production of RANKL and IL6. [Cancer Cell] Abstract | Graphical Abstract

Interactions of Renal-Clearable Gold Nanoparticles with Tumor Microenvironments: Vasculature and Acidity Effects

Researchers investigated the accumulation of ultrasmall renal-clearable gold NPs (AuNPs) with and without acidity targeting in xenograft mouse models of two prostate cancer types, PC-3 and LNCaP, with distinct microenvironments. Their results showed that both sets of AuNPs could easily penetrate into the tumors but their uptake and retention were mainly dictated by the tumor microvasculature and the enhanced permeability and retention effect over the entire targeting process. [Angew Chem Int Ed] Abstract

Diagnosis of Prostate Cancer by Desorption Electrospray Ionization Mass Spectrometric Imaging of Small Metabolites and Lipids

Investigators performed desorption electrospray ionization mass spectrometry imaging on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, their method included Krebs cycle intermediates, which they found to be highly informative in distinguishing cancer from benign tissue. [Proc Natl Acad Sci USA] Abstract

PSMA Redirects Cell Survival Signaling from the MAPK to the PI3K-AKT Pathways to Promote the Progression of Prostate Cancer

Scientists generated mice bearing prostate-specific membrane antigen (PSMA)-positive or PSMA-negative prostate cancer (PCa) by crossing PSMA-deficient mice with transgenic PCa models, enabling direct assessment of PCa incidence and progression in the presence or absence of PSMA. Relative to PSMA-positive tumors, tumors lacking PSMA had less than half the abundance of type 1 insulin-like growth factor receptor, less activity in the survival pathway mediated by PI3K-AKT signaling, and more activity in the proliferative pathway mediated by MAPK-ERK1/2 signaling. [Sci Signal] Abstract

Antagonizing Effects of Membrane-Acting Androgens on the Eicosanoid Receptor OXER1 in Prostate Cancer

Researchers showed that androgens can specifically act at the membrane level via the GPCR oxoeicosanoid receptor 1 (OXER1) in prostate cancer cells. OXER1 expression paralleled that of membrane androgen binding in prostate cancer cell lines and tumor specimens, while in silico docking simulation of OXER1 showed that testosterone could bind to OXER1 within the same grove as 5-OxoETE, the natural ligand of OXER1. [Sci Rep] Full Article

ELF5-Mediated AR Activation Regulates Prostate Cancer Progression

Investigators found that the E74-like factor 5 (ELF5) is frequently expressed in androgen receptor (AR) activated prostate cancer cells, where it binds to AR acting as a physiological partner and negatively regulates its transcriptional activity. [Sci Rep] Full Article

MicroRNA-802 Inhibits Epithelial-Mesenchymal Transition through Targeting Flotillin-2 in Human Prostate Cancer

Researchers identified the functional roles of miR-802 in regulating epithelial–mesenchymal transition in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines by qRT-PCR. [Biosci Rep] Full Article

CLINICAL RESEARCH

Adding Celecoxib with or without Zoledronic Acid for Hormone-Naïve Prostate Cancer: Long-Term Survival Results from an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial

Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy was a randomized controlled trial using a multiarm, multistage, platform design. It recruited men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. The authors report survival data for two celecoxib-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival. [J Clin Oncol] Full Article

Germline Mutations in the Kallikrein 6 Region and Predisposition for Aggressive Prostate Cancer

Scientists surveyed the Kallikrein (KLK) region for single-nucleotide polymorphisms associated with aggressive prostate cancer (PCa) in 1858 PCa patients. Several single-nucleotide polymorphisms in very strong linkage disequilibrium in the KLK6 region and located within the same haplotype, identified individuals at increased risk of aggressive PCa in both discovery and validation cohorts. [J Natl Cancer Inst] Abstract | Press Release

Contrasting Roles of the ABCG2 Q141K Variant in Prostate Cancer

The authors report that in patients with recurrent prostate cancer, those who carry the ABCG2 Q141K variant had a significantly shorter time to PSA recurrence post-prostatectomy than patients homozygous for wild-type ABCG2. Transport studies showed that wild-type ABCG2 was able to efflux more folic acid than the Q141K variant, suggesting that retained tumoral folate contributes to the decreased time to PSA recurrence in the Q141K variant patients. [Exp Cell Res] Abstract

Immune Mediators in the Tumor Microenvironment of Prostate Cancer

Researchers highlight the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy. [Chin J Cancer] Full Article

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Exact Imaging Announces Health Canada Approval and License for Its ExactVu™ Micro-Ultrasound System for Prostate Imaging and Biopsy

Exact Imaging announced it has received Health Canada approval and the corresponding medical device license to sell its ExactVu™ high resolution micro-ultrasound system. [Exact Imaging] Press Release

Major Pharmaceutical Companies Collaborate in Groundbreaking NCCN Project

The National Comprehensive Cancer Network^® (NCCN^®) Oncology Research Program has funded three studies in its first multi-industry collaborative research project in which Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company are collaborating with NCCN^® to study combination therapeutic agents in lung cancer and head and neck cancers. [National Comprehensive Cancer Network] Press Release

US Science Agencies Face Deep Cuts in Trump Budget

When it comes to science, there are few winners in US President Donald Trump’s first budget proposal. The plan outlines double-digit cuts for the Environmental Protection Agency and the National Institutes of Health. It also lays the foundation for a broad shift in the United States’ research priorities, including sharp decreases to environmental and climate programs. [Nature News] Editorial

United Kingdom Moves Forward with Controversial Embryo Technique

Making heritable genetic changes to eggs and sperm was prohibited in the United Kingdom until Parliament approved a new law allowing the technique in 2015. In December 2016, the Human Fertilization and Embryo Authority announced that it would be willing to grant a license to use the technique in patients. The Telegraph reported that the agency has granted its first license to Newcastle University, where researchers have been working on lab-based experiments for years. [ScienceInsider] Editorial

Pasteur Institute’s Scientists Make Last-Ditch Plea to Keep Their President

Following a string of failed attempts to keep their president Christian Bréchot on after he reaches the mandated retirement age, leading researchers have continued to agitate quietly in his favor — even though the institute’s board of directors has made what seems to be a final decision on the matter and is starting a search for Bréchot’s successor. [Nature News] Editorial

NEW GRKs and Arrestins: From Structure to Disease
June 11-16, 2017
Saxtons River, United States

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NEW Postdoctoral Fellow – Prostate Cancer Research (Vancouver Prostate Center)

NEW Faculty Position – Urologic Pathology (University of California Los Angeles)

NEW Postdoctoral Fellow – Computational Cancer Biology (European Molecular Biology Laboratory)

PhD Student – Prostate Cancer Research (Vancouver Prostate Center)

Postdoctoral Research Fellow – Urological Cancers (Institute of Cancer Research)

Postdoctoral Position – Genomics and Molecular Biology (The George Washington University)

PhD Studentships – Translational Research Network for Prostate Cancer (University of Glasgow)

Postdoctoral Researcher – Prostate Cancer Immunotherapy (University of Chicago)

Postdoctoral Fellow – Prostate Cancer Biology (Weill Cornell Medicine)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College / Geisel School of Medicine)

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