Prostate Cell News Volume 7.46 | Dec 16 2016

TOP STORY

Ailanthone Targets p23 to Overcome MDV3100 Resistance in Castration-Resistant Prostate Cancer

Researchers identified the small molecule Ailanthone (AIL) as a potent inhibitor of both full-length androgen receptor (AR) and constitutively active truncated AR splice variants. AIL binds to the co-chaperone protein p23 and prevents AR’s interaction with HSP90, thus resulting in the disruption of the AR-chaperone complex followed by ubiquitin/proteasome-mediated degradation of AR as well as other p23 clients including AKT and Cdk4, and downregulates AR and its target genes in PCa cell lines and orthotopic animal tumors. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Inhibition of Notch Pathway Arrests PTEN-Deficient Advanced Prostate Cancer by Triggering p27-Driven Cellular Senescence

Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, investigators demonstrated that Pten-deficient prostate tumors are addicted to the NOTCH signaling. Importantly, they found that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumors by triggering cellular senescence. [Nat Commun] Full Article

Transcriptional Regulation of Core Autophagy and Lysosomal Genes by the Androgen Receptor Promotes Prostate Cancer Progression

Scientists identified four core autophagy genes: ATG4B, ATG4D, ULK1, and ULK2, in addition to the transcription factor TFEB, a master regulator of lysosomal biogenesis and function, as transcriptional targets of androgen receptor in prostate cancer. [Autophagy] Abstract

Inhibition of KPNA4 Attenuates Prostate Cancer Metastasis

The authors report a novel correlation between karyopherin α4 (KPNA4) and prostate cancer (PCa) pathological stages. KPNA4 mediates the cytoplasm-to-nucleus translocation of transcription factors, including nuclear factor kappa B, although its role in PCa was largely unknown. They found that knockdown of KPNA4 reduces cell migration in multiple PCa cell lines, suggesting a role of KPNA4 in PCa progression. [Oncogene] Abstract

6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-Androgen Receptor Therapy in Prostate Cancer Cells

Using high-throughput small-molecule screening, researchers found that the small molecule 6-bromo-indirubin-3′-oxime (6BIO) significantly improves the targeting of antisense oligonucleotides delivered by gymnosis (i.e., in the absence of any transfection reagents) in both the cell cytoplasm and the nucleus. [Mol Ther] Abstract

ERK-Mediated NF-κB Activation through ASIC1 in Response to Acidosis

Investigators showed that among four prostate cancer cell lines tested, 22Rv1 cells express the highest level of phosphorylated AKT that is not impacted by acidosis. However, acidosis can still induce nuclear factor-κB (NF-κB) activation during which extracellular signal-regulated kinase (ERK) serves as an alternative pathway for acid-sensing ion channel 1 (ASIC)-mediated cell signaling. [Oncogenesis] Full Article

GABARAPL1 Suppresses Metastasis by Counteracting PI3K/Akt Pathway in Prostate Cancer

Using a genome wide shRNA screen, scientists identified GABARAPL1 as a potential prostate cancer metastasis suppressor. [Oncotarget] Full Article

Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis

The authors focused on the effect of pioglitazone (PGZ) on prostate carcinogenesis using a transgenic rat for an adenocarcinoma of prostate model. Adenocarcinoma lesions as a percentage of overall lesions in the ventral prostate were significantly reduced by PGZ treatment in a dose-dependent manner. The number of adenocarcinomas per given area in the ventral prostate was also significantly reduced by PGZ treatment. [Int J Mol Sci] Full Article

Long Intragenic Non-Coding RNA LincRNA-p21 Suppresses Development of Human Prostate Cancer

Investigators aimed to study the roles of lincRNA-p21 in development of human prostate cancer. Expression of lincRNA-p21 was assessed by real-time PCR in cell lines and in human tissues. Lentivirus carrying sh-lincRNA-p21, lincRNA-p21 or control constructs were used to determine their effects on cell proliferation and apoptosis. A mouse xenograft model was employed to explore the functions of lincRNA-p21 on cancer cell population growth in vivo. [Cell Prolif] Abstract

CLINICAL RESEARCH

Conditionally Reprogrammed Normal and Primary Tumor Prostate Epithelial Cells: A Novel Patient-Derived Cell Model for Studies of Human Prostate Cancer

Using conditional reprogramming (CR), researchers established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patient’s prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype. [Oncotarget] Full Article

Histone Demethylase Lysine Demethylase 5B in Development and Cancer

Recent studies showed that lysine demethylase 5B, also called JARID1B or PLU-1 (KDM5B) expression was increased in breast, bladder, lung, prostate and many other tumors and promotes tumor initiation, invasion and metastasis. Given its association with tumor progression and prognosis of cancer patients, KDM5B was proposed to be a novel target for the prevention and treatment of human cancers. In this review, researchers summarize recent advances in understanding of the regulation and function of KDM5B in development and cancer. [Oncotarget] Full Article

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

Pfizer and Astellas Announce Top-Line Results from Phase IV PLATO Trial of XTANDI^® (enzalutamide) Capsules in Patients with Metastatic Castration-Resistant Prostate Cancer

Pfizer Inc. and Astellas Pharma Inc. announced the Phase IV PLATO study, evaluating the efficacy and safety of continued treatment with XTANDI^® (enzalutamide), plus abiraterone acetate and prednisone as compared to treatment with abiraterone acetate and prednisone alone, did not meet its primary endpoint of improvement in progression-free survival in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer whose prostate-specific antigen has previously progressed on XTANDI. [Pfizer Inc.] Press Release

Cancer Targeted Technology Commences Phase I Clinical Trial of CTT1057, a Diagnostic Imaging Agent for Prostate Cancer

Cancer Targeted Technology (CTT) announced that a Phase I clinical trial has commenced in men with high risk metastatic prostate cancer. [Cancer Targeted Technology (Business Wire, Inc.)] Press Release

Zenith Announces Initiation of Phase Ib Clinical Combination Trial for ZEN-3694

Zenith Capital Corp. announced that its wholly owned subsidiary, Zenith Epigenetics Ltd., has initiated a Phase Ib clinical trial in metastatic castration resistant prostate cancer (mCRPC) patients, dosing ZEN-3694 in combination with enzalutamide. In this Phase Ib trial, Zenith Epigenetics will be evaluating the safety, pharmacokinetics, and efficacy of ZEN-3694 in combination with, enzalutamide (Xtandi) in mCRPC patients that have progressed on first-line standard-of-care anti-androgen therapy. [Zenith Capital Corp. (PR Newswire Association LLC)] Press Release

Scottish Medicines Consortium Approves Sanofi Prostate Cancer Drug

Sanofi Genzyme announced that the Scottish Medicines Consortium has accepted Jevtana^® (cabazitaxel) for routine use in NHS Scotland for the treatment of metastatic hormone-refractory prostate cancer. [Sanofi-Genzyme Bioventures (PR Newswire Association LLC.)] Press Release

United Kingdom Gives Green Light for Mitochondrial Replacement Technique

Authorities in the United Kingdom have given the go-ahead for mitochondrial replacement therapy, a new type of assisted reproduction that could allow some families to avoid passing on genetic disease. The technique is controversial because it combines genetic material from three people: two eggs and one sperm. The decision has been widely anticipated. It comes after years of debate and a change in the country’s laws passed by Parliament in 2015 [Science Insider] Editorial

NIH Discusses Curbing Lab Size to Fund More Midcareer Scientists

A new analysis by the National Institutes of Health in Bethesda, Maryland, reinforces previous studies showing that productivity may lag as labs get bigger. The results suggest that NIH could fund thousands more researchers without any drop-off in scientific output if it capped the total number of grants an investigator could receive, an NIH official says. [Science Insider] Editorial

Is Donald Trump Pushing More Scientists towards Political Activism?

Around the world, individual researchers and representatives of scientific societies are signing letters of protest or advice, offering to counsel Trump’s transition team and ramping up efforts to communicate the value of science to the public. [Nature News] Editorial

Canada’s Government Scientists Get Antimuzzling Clause in Contract

Scientists working for the Canadian government have successfully negotiated a clause in their new contract that guarantees their right to speak to the public and the media about science and their research, without needing approval from their managers. [ScienceInsider] Editorial

NEW Mouse Development, Stem Cells & Cancer
June 7-26, 2017
Cold Spring Harbor, United States

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

NEW Associate Member – Stem Cell/Gene Therapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Researcher – Prostate Cancer (Icahn School of Medicine at Mount Sinai)

Postdoctoral Researcher – Prostate Carcinogenesis (The University of Alabama)

Postdoctoral Researcher – Prostate Cancer (Cleveland Clinic Lerner Research Institute)

Postdoctoral Fellow – Molecular Oncology (Institute of Oncology Research)

Faculty Position – Cancer Immunology (University of New Mexico School of Medicine)

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

Faculty Position – Cancer Immunology (University of New Mexico)

Postdoctoral Fellowship – Cancer Biology (The University of Maryland)

Assistant, Associate or Full Professor – Cancer Biology (University of Pennsylvania)

Postdoctoral Associate – Cancer Research (University of Minnesota)

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.