Prostate Cell News Volume 9.44 | Nov 16 2018

TOP STORY

Proteostasis by STUB1/HSP70 Complex Controls Sensitivity to Androgen Receptor Targeted Therapy in Advanced Prostate Cancer

Androgen receptor (AR)/AR-V7 proteostasis required the interaction of E3 ubiquitin ligase STUB1 and HSP70 complex. STUB1 disassociated AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 significantly inhibited prostate tumor growth and improved enzalutamide/abiraterone treatments through AR/AR-V7 suppression. [Nat Commun] Full Article

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Targeting AR-Beclin 1 Complex-Modulated Growth Factor Signaling Increases the Antiandrogen-Enzalutamide Sensitivity to Better Suppress the Castration-Resistant Prostate Cancer Growth

Researchers found the expression of beclin 1 was decreased in both enzalutamide (Enz)-resistant cell lines as compared to their parental Enz-sensitive cells, and targeting beclin 1 could lead to increased Enz-sensitivity in these two castration-resistant prostate cancer cell lines. [Cancer Lett] Abstract

CCL2 Induces Resistance to the Antiproliferative Effect of Cabazitaxel in Prostate Cancer Cells

The stimulation of DU145 cells with C-C motif chemokine ligand 2 (CCL2) increased the proliferation rate under treatments with cabazitaxel, and a specific receptor of CCL2 antagonist suppressed the proliferation of DU145-TxR and DU145-TxR/CxR cells under treatments of cabazitaxel. [Cancer Sci] Abstract

Alternative RNA Splicing of the GIT1 Gene Is Associated with Neuroendocrine Prostate Cancer

The authors showed that G protein-coupled receptor kinase-interacting protein 1 (GIT1)-A and GIT1-C regulated differential transcriptomes in prostate cancer cells, where GIT1-A was enriched with genes associated with cell morphogenesis and neural functions. [Cancer Sci] Abstract

Epithelial Cell Adhesion Molecule (EpCAM) Is Involved in Prostate Cancer Chemotherapy/Radiotherapy Response In Vivo

EpCAM was knocked down in the PC-3 CaP cell line using short hairpin RNA. The effect of EpCAM-knockdown (KD) on tumor growth, chemo/radiotherapy response and animal survival was evaluated on subcutaneous and orthotopic mouse models. Researchers demonstrated that KD of EpCAM was associated with downregulation of the PI3K/Akt/mTOR pathway. [BMC Cancer] Full Article

The Determination of the Potential Anticancer Effects of Coriandrum sativum in PC-3 and LNCaP Prostate Cancer Cell Lines

The effects of C. sativum extract on gene expression, viability, colony formation, migration, and invasion of PC-3 and LNCaP prostate cancer cell lines were investigated. Scientists showed that C. sativum extract decreased colony formation while inhibiting cell invasion and migration. [J Cell Biochem] Abstract

TROAP Regulates Prostate Cancer Progression via the WNT3/Survivin Signaling Pathways

Gene interference with lentivirus was used to silence trophinin associated protein (TROAP) expression in prostate cancer (PCa) cells and knockdown efficiency was detected by qRT-PCR and western blot analysis. Cell viability, colony formation, cell cycle and apoptosis were then assessed to determine the function of TROAP in PCa cells. [Oncol Rep] Abstract

Radiobiological Characterization of ⁶⁴CuCl₂ as a Simple Tool for Prostate Cancer Theranostics

Using a panel of prostate cancer cell lines in comparison with a non-tumoral prostate cell line, investigators combined cytogenetic approaches with radiocytotoxicity assays to obtain significant insights into the cellular consequences of exposure to ⁶⁴CuCl₂. [Molecules] Full Article | Graphical Abstract

Inhibition of miR-423-5p Suppressed Prostate Cancer through Targeting GRIM-19

Inhibition of miR-423-5p suppressed PC3 cell proliferation, promoted PC3 cell apoptosis, and decreased anti-apoptosis protein BCL-2 expression. GRIM-19 was a target of miR-423-5p, and GRIM-19 was negatively regulated by miR-423-5p in PC3 cells. In addition, miR-423-5p knockdown inhibited the proliferation and promoted the apoptosis of PC3 cells through GRIM-19. [Gene] Abstract

Long Noncoding RNA IGF2AS Is Acting as an Epigenetic Tumor Suppressor in Human Prostate Cancer

IGF2AS was downregulated in both prostate cancer (PCa) cell lines and human PCa tumors. In VCaP and PC3 cells, lentivirus-induced IGF2AS overexpression suppressed cancer cell proliferation and invasion in vitro, and xenograft development in vivo. IGF2 was downregulated by IGF2AS overexpression. Conversely, IGF2 upregulation reverted the suppressing function of IGF2AS on PCa proliferation and invasion. [Urology] Abstract

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Emerging Cell Cycle Inhibitors for Treating Metastatic Castration-Resistant Prostate Cancer

Recent evidence of genomic heterogeneity and sensitivity to PARP inhibitors supports investigation of targeted agents in castration-resistant prostate cancer. Cell cycle inhibitors are therefore logical molecules to investigate. Review of the current literature identified cell cycle inhibitors under study in early phase clinical trials targeting the G1, S, G2 and M phases of the cell cycle. [Expert Opin Emerg Drugs] Abstract

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NOX to Present Clinical Data

Noxopharm (NOX) announced that it is presenting two posters. This first presentation provides an update on the company’s ongoing open-label Phase Ib study evaluating Veyonda^® in combination with palliative external beam radiotherapy in men with metastatic castrate-resistant prostate cancer. [Press release from Noxopharm discussing research presented at the 45^th Annual Meeting of the Clinical Oncology Society of Australia (COSA), Perth] Press Release

Constellation Pharmaceuticals Highlights EZH2 Inhibition Program in Prostate Cancer

Constellation Pharmaceuticals, Inc. presented on its EZH2 inhibition program in prostate cancer. [Press release from Constellation Pharmaceuticals, Inc. discussing research presented at the EORTC/NCI/AACR Molecular Targets and Cancer Therapeutics Symposium, Dublin] Press Release

RadioMedix and Orano Med Receive FDA Orphan Drug Designation for AlphaMedix^™ for the Treatment of Neuroendocrine Tumors

RadioMedix Inc. and Orano Med announced that the FDA has granted Orphan Drug Designation to AlphaMedix^™ for the treatment of neuroendocrine tumors. [RadioMedix Inc.] Press Release

Janssen Receives Positive CHMP Opinion for ERLEADA^™ (Apalutamide) for Patients with Non-Metastatic Castration-Resistant Prostate Cancer Who Are at High Risk of Developing Metastatic Disease

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion for apalutamide, a next generation oral androgen receptor inhibitor for the treatment of adult patients with non-metastatic castration-resistant prostate cancer who are at high risk of developing metastatic disease. [Janssen Global Services, LLC] Press Release

Veru Advances Novel, First-in-Class Oral Tubulin Inhibitor for Refractory Metastatic Prostate Cancer

Veru Inc. announced that it has submitted an Investigational New Drug application with the FDA for VERU-111, a first-in-class, next generation, proprietary, oral tubulin inhibitor for the treatment of refractory metastatic prostate cancer. [Veru Inc.] Press Release

STEM Candidates Elected to U.S. House Prepare for Their New Jobs

They’ve won their elections and are headed to Washington, D.C. Their next challenge is using their expertise to make Congress work better. [ScienceInsider] Editorial

Dartmouth Faces Lawsuit Over Sexual Misconduct by Professors

Seven women filed a $70 million lawsuit against Dartmouth College over its alleged role in allowing a toxic culture to form, which led to harassment, discrimination, and assault. The lawsuit argues that the university failed to protect its students from misconduct, which in two cases included rape, The Chronicle of Higher Education reports. [The Scientist] Editorial

Brexit: What the Draft Deal Means for Science

After two years of negotiations, the first real glimmers of what Brexit might involve have emerged. On 14 November, the Cabinet, the UK government’s senior decision-making body, backed a draft agreement on the terms of the country’s withdrawal from the European Union. For science, many of the details that will be most relevant are still to be thrashed out. [Nature News] Editorial

NEW AACR International Conference New Horizons in Cancer Research
May 3-5, 2019
Shenzhen, China

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NEW Faculty & Leadership Positions- Cancer-Focused Target & Drug Discovery (The University of New Mexico)

Postdoctoral Associate – Molecular and Cell Biology (Baylor College of Medicine)

Postdoctoral Fellow – Advanced Prostate Cancer Research (Cleveland Clinic)

Postdoctoral Fellow/Research Associate Positions – Cell Immortalization (Gerogetown University Medical Center)

Postdoctoral Position – Translational Cancer Research (University of California San Francisco)

Posdoctoral Position – Prostate Cancer Research (Louisiana State University Health Sciences Center)

Group Leader – Cancer Biology and/or Therapy (Institute of Oncology Research Universita della Svizzera Italiana)

PhD Studentships – Cancer Research (The Cancer Research UK Manchester Institute)

Postdoctoral Fellow – Cancer Immunotherapy (University of Notre Dame)

Postdoctoral Fellow – Prostate Disease Research (Henry M. Jackson Foundation for the Advancement of Military Medicine)

Assistant/Associate/Professor – Cancer Biology (University of Cincinnati)

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

Research Fellow – Prostate Cancer (Sechenov University)

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