Prostate Cell News Volume 9.30 | Aug 10 2018

TOP STORY

Nuclear Gatekeeper Could Block Undruggable Prostate Cancer Targets

Blocking nuclear gateways that traffic cancer-promoting molecules to nucleus, could offer a new way to target aggressive cancer. [Press release from Thomas Jefferson University discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

BMI1 Drives Metastasis of Prostate Cancer in Caucasian and African-American Men and Is a Potential Therapeutic Target: Hypothesis Tested in Race-Specific Models

The authors investigated the relevance of BMI1 in metastatic prostate cancer (CaP) disease in Caucasian and African-Americans. They employed race-specific CaP models, clinical specimens, clinical data mining, gene-microarray, transcription-reporter assay, chromatin-immunoprecipitation, immunohistochemistry, transgenic- zebrafish and mouse metastasis models. [Clin Cancer Res] Abstract

Novel CIL-102 Derivatives as Potential Therapeutic Agents for Docetaxel-Resistant Prostate Cancer

Scientists modified the structure of CIL-102 and investigated the efficacy of the derivatives against castration-resistant prostate cancer (CRPC) and docetaxel-resistant prostate cancer (PCa). These novel CIL-102 derivatives inhibited CRPC tumorigenicity, including proliferation, migration and colony formation, and importantly, selectively inhibited CRPC cell proliferation over non-cancerous prostate epithelia. [Cancer Lett] Abstract

The RNA-Binding Protein PCBP1 Functions as a Tumor Suppressor in Prostate Cancer by Inhibiting Mitogen Activated Protein Kinase 1

Attenuation of mitogen activated protein kinase 1 (MAPK1) inhibited in vitro and in vivo tumorigenicity and metastasis in prostate cancer cell line, PC3. Overexpression of MAPK1 in the PC3 cells increased the tumorigenicity and metastasis. [Cell Physiol Biochem] Full Article

CD38 Inhibits Prostate Cancer Metabolism and Proliferation by Reducing Cellular NAD⁺ Pools

Researchers demonstrated a novel connection between CD38, modulation of NAD⁺, and tumor cell metabolism in prostate cancer (PCa). CD38 expression inversely correlated with PCa progression. Expressing CD38 in PCa cells lowered intracellular NAD⁺, resulting in cell cycle arrest and expression of p21Cip1. [Mol Cancer Res] Abstract

MRGBP Promotes AR-Mediated Transactivation of KLK3 and TMPRSS2 via Acetylation of Histone H2A.Z in Prostate Cancer Cells

Investigators showed that MRG domain binding protein (MRGBP) promoted growth of androgen receptor (AR)-positive prostate cancer cells. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. [Biochim Biophys Acta] Abstract

Inhibition of Cholesterol Biosynthesis Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer (CRPC)

Scientists found that HMG-CoA reductase (HMGCR), a crucial enzyme in the mevalonate pathway for sterol biosynthesis, is elevated in enzalutamide-resistant prostate cancer cell lines. HMGCR knockdown could re-sensitize these cells to the drug, and HMGCR overexpression conferred resistance to it, suggesting that aberrant HMGCR expression is an important enzalutamide resistance mechanism in prostate cancer cells. [J Biol Chem] Abstract | Full Article

Novel Role of Giα2 in Cell Migration: Downstream of PI3‐Kinase-AKT and Rac1 in Prostate Cancer Cells

Researchers investigated the interactions among G‐protein coupled receptor, Giα2, PI3‐kinase, and Rac1 activation in the induction of migratory and invasive behavior by diverse stimuli. Knockdown and knockout of endogenous Giα2 in PC3 cells resulted in attenuation of transforming growth factor β1, oxytocin, SDF‐1α, and epidermal growth factor effects on cell migration and invasion. [J Cell Physiol] Abstract

A Membrane Fusion Protein, Ykt6, Regulates Epithelial Cell Migration via MicroRNA-Mediated Suppression of Junctional Adhesion Molecule A

Investigators found that Ykt6 acts as a negative regulator of migration and invasion of human prostate epithelial cells. Furthermore, Ykt6 regulated the integrity of epithelial adherens and tight junctions. The observed anti-migratory activity of Ykt6 was mediated by a unique mechanism involving the expressional upregulation of microRNA 145, which selectively decreased the cellular level of junctional adhesion molecule A. [Cell Cycle] Abstract

CRMP4a Suppresses Cell Motility by Sequestering RhoA Activity in Prostate Cancer Cells

Collapsin response mediator protein 4a (CRMP4a) overexpression largely reduced while CRMP4a knockdown remarkably increased cytoskeletal organization in PC-3 cells. CRMP4a immunoprecipitation pulled down RhoA but not cdc42 or Rac1 proteins. Manipulating CRMP4a expression levels reversely altered active RhoA levels. [Cancer Biol Ther] Abstract

Parallel Study on Protein O-GlcNAcylation in Prostate Cancer Cell with a Sensitive Microarray Biochip

The authors developed a powerful microarray platform for a sensitive, specific and high-throughput analysis of protein O-GlcNAcylation. The developed array biochip was then utilized to parallelly analyze the O-GlcNAcylation of three oncogenic transcription factors C-Myc, NF-κB and p53 in normal prostate epithelial cell and prostate cancer cell line. [Anal Biochem] Abstract

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Current Status of Androgen Receptor-Splice Variant 7 Inhibitor Niclosamide in Castrate-Resistant Prostate-Cancer

The authors outline the most recent pre- and clinical- data on the current status of niclosamide in the treatment of ARV7-positive castrate resistant prostate cancer patients. [Invest New Drugs] Abstract

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$1.3 Million to Address Prostate Cancer and Male Infertility

The Australian Government will provide medical research funding for prostate cancer and infertility, marking the first step towards a new National Male Health Strategy. [Commonwealth of Australia] Press Release

Harpoon Therapeutics Treats First Patient with HPN424 in Phase I Clinical Trial of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients

Harpoon Therapeutics announced that the first patient has been treated with HPN424 in a Phase I clinical study of mCRPC patients. HPN424 is the first of multiple compounds in development that are based on the company’s Tri-specific T cell Activating Construct platform and designed to penetrate solid tumors, have extended serum half-life, and recruit patients’ own T cells to destroy malignant tumor cells. [Harpoon Therapeutics] Press Release

US Congress Leaves Science Agencies Hanging — Again

Lawmakers in the US Congress are running out of time to pass a budget for the 2019 fiscal year, and have yet to resolve major disagreements over climate-change and environment programs. [Nature News] Editorial

Gottlieb: FDA Will Streamline Drug Safety Evaluations

The FDA will soon standardize the way it handles data on the safety and effectiveness of drugs in an effort to reduce inconsistencies in the drug review process. [STAT News] Editorial

NEW The Tumor Cell: Plasticity, Progression and Therapy
March 3-6, 2019
New York, New York, United States

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NEW Postdoctoral Fellow/Research Scientist – Prostate Cancer (Università della Svizzera italiana)

Research Fellow – Personalized Medicine of Anti-Cancer Therapy (Mayo Clinic)

Senior Research Scientist – Prostate Cancer Research (University of California, San Francisco)

Postdoctoral Position – Prostate Cancer (The University of Minnesota, Twin Cities)

Clinical Fellow – Prostate Cancer Biology (Cancer Research UK Manchester Institute)

Assistant or Associate Professor – Prostate Cancer (Lerner Research Institute of the Cleveland Clinic)

Postdoctoral Position – Tumor Ecosystem Research (University of Zurich)

Postdoctoral Felllow – Non-Coding RNA & Cancer Research (University of Toronto)

Research Fellowship – Prostate Cancer Pathology (Weill Cornell Medicine)

Postdoctoral Fellow – Prostate Cancer Metastasis Research (Oregon Health & Science University)

Postdoctoral Fellow – Molecular Mechanisms of Prostate Cancer (Northwestern University Feinberg School of Medicine)

Postdoctoral Fellow – Prostate Cancer Development & Progression Research (Brigham & Women’s Hospital-Harvard Medical School)

Research Fellow – Prostate Cancer (Sechenov University)

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