Mammary Cell News Volume 10.21 | May 31 2018

TOP STORY

Targeting p38α Increases DNA Damage, Chromosome Instability, and the Anti-Tumoral Response to Taxanes in Breast Cancer Cells

Decreased p38α signaling resulted in impaired ATR activation and homologous recombination repair, with concomitant increases in replication stress, DNA damage, and chromosome instability, leading to cancer cell death and tumor regression. [Cancer Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer

Glycolysis restriction repressed the expression of a specific CCAAT/enhancer-binding protein beta (CEBPB) isoform, liver-enriched activator protein (LAP), via the AMP-activated protein kinase-ULK1 and autophagy pathways, whereas LAP controled granulocyte colony-stimulating factor (CSF) and granulocyte macrophage-CSF expression to support myeloid-derived suppressor cell development. [Cell Metab] Abstract | Graphical Abstract

Small Molecule Targeted Recruitment of a Nuclease to RNA

A small molecule that selectively bound the oncogenic miR-96 hairpin precursor was appended with a short 2′-5′ poly(Archive) oligonucleotide. The conjugate locally activated endogenous, latent ribonuclease, which selectively cleaved the miR-96 precursor in cancer cells in a catalytic and sub-stoichiometric fashion. Silencing miR-96 derepressed pro-apoptotic FOXO1 transcription factor, triggering apoptosis in breast cancer, but not healthy breast cells. [J Am Chem Soc] Abstract | Press Release | Graphical Abstract

IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer

Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) stabilized the mRNA of an alternative WNT ligand (WNT5B) indirectly by repressing miR145-5p, which targets WNT5B, resulting in TAZ activation by alternative WNT signaling. IMP3 also facilitated the transcription of SLUG, which is necessary for TAZ nuclear localization and activation, by a mechanism that is also mediated by WNT5B. [Cell Rep] Full Article | Graphical Abstract

An Androgen Receptor Negatively Induced Long Non-Coding RNA ARNILA Binding to miR-204 Promotes the Invasion and Metastasis of Triple-Negative Breast Cancer

The authors demonstrated that androgen receptor negatively induced long non-coding RNA (ARNILA) functioned as a competing endogenous RNA for miR-204 to facilitate expression of its target gene Sox4, which is known to induce epithelial-mesenchymal transition (EMT) and contribute to breast cancer progression, thereby promoting EMT, invasion and metastasis of triple-negative breast cancer. [Cell Death Differ] Abstract

Betulinic Acid Chemosensitizes Breast Cancer by Triggering ER Stress-Mediated Apoptosis by Directly Targeting GRP78

Researchers identified glucose-regulated protein 78 (GRP78) as the direct interacting target of betulinic acid (BA). BA administration significantly elevated GRP78-mediated endoplasmic reticulum (ER) stress and resulted in the activation of protein kinase R-like ER kinase/eukaryotic initiation factor 2a/CCAAT/enhancer-binding protein homologous protein apoptotic pathway. [Cell Death Dis] Full Article

Heat Shock Factor 1 Confers Resistance to Lapatinib in ERBB2-Positive Breast Cancer Cells

Investigators found that multiple adaptive receptor tyrosine kinases were activated in lapatinib-resistant cells in vivo, some of which have been previously described (Axl, MET) and some of which were novel (PDGFRα, PDGFRβ, VEGFR1, MUSK, NFGR). All lapatinib-resistant cells showed chronically activated heat shock factor 1 and its transcriptional targets, heat shock proteins, and, as a result, superior tolerance to proteotoxic stress. [Cell Death Dis] Full Article

Enhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth

Scientists found Zn²⁺-dependent Ca²⁺ release, mediated by ZnR/GPR39 activity, in TAMR tamoxifen-resistant cells derived from MCF-7 cells, but not in estrogen receptor-expressing MCF-7 or T47D cells. Expression of ZnR/GPR39 was increased in grade 3 human breast cancer biopsies compared to grade 2. Activation of ZnR/GPR39 in TAMR cells triggered MAPK, mTOR and PI3K signaling. [Sci Rep] Full Article

NOTCH3 Inactivation Increases Triple Negative Breast Cancer Sensitivity to Gefitinib by Promoting EGFR Tyrosine Dephosphorylation and Its Intracellular Arrest

Notch3 was able to regulate activated epidermal growth factor receptor (EGFR) membrane localization into lipid raft microdomains, as Notch3 inhibition, such as raft depletions, induced EGFR internalization and its intracellular arrest, without involving receptor degradation. These events were associated with the EGFR tyrosine dephosphorylation at Y1173 residue (but not at Y1068) by the protein tyrosine phosphatase H1, thus suggesting its possible involvement in the observed Notch3-dependent triple-negative breast cancer sensitivity response to gefitinib. [Oncogenesis] Full Article

Delivery of Mitochondriotropic Doxorubicin Derivatives Using Self-Assembling Hyaluronic Acid Nanocarriers in Doxorubicin-Resistant Breast Cancer

Compared with free doxorubicin (DOX), hyaluronic acid-ionic-triphenylphosphonium-DOX produced much greater intracellular DOX accumulation and mitochondrial localization, leading to increased ROS production, slightly decreased mitochondrial membrane potential, increased cytotoxicity in MCF-7/ADR cells and enhanced tumor targeting in vivo. [Acta Pharmacol Sin] Abstract

Checkpoint Blockade in the Treatment of Breast Cancer: Current Status and Future Directions

The authors discuss the current evidence for PD-1/PD-L1 blockade in metastatic triple-negative breast cancer, HER2⁺ breast cancer and ER⁺ disease, as well as the emerging evidence for use in the early-stage (neoadjuvant) setting. They also propose potential ways of improving responses to checkpoint blockade in breast cancer. [Br J Cancer] Abstract

Androgen Blockade Based Clinical Trials Landscape in Triple Negative Breast Cancer

Androgen receptor targeted treatment has shown promising preliminary results in triple negative breast cancer. Research investigating androgen-blockade based combination therapy in this aggressive tumor has demonstrated promising benefit in preclinical studies, and comparable clinical trials of combined strategies with CDK4/6 inhibitors, PI3K inhibition, chemotherapy, and immunotherapy, are ongoing. [Biochim Biophys Acta] Abstract

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

Circulating Tumor Cells to Help Stage Metastatic Breast Cancer, New Research to be Featured

Menarini Silicon Biosystems announced that a new study has found that using circulating tumor cells, a form of liquid biopsy, holds promise as a key tool for developing a staging system that can have a significant impact in the treatment of metastatic breast cancer. [Press release from Menarini Silicon Biosystems discussing research to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Key Studies Demonstrate MammaPrint^® and BluePrint’s^® Utility in Personalizing Neoadjuvant Treatment Approaches for Early-Stage Breast Cancer Patients

Agendia, Inc., announced two studies scheduled to be presented. [Press release from Agendia Inc. discussing research to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Huntsman Cancer Institute and TGen Receive $6.7 Million Grant to Battle a Hidden Enemy

In an effort to combat metastatic breast cancer, the U.S. Department of Defense has jointly awarded a $6.7 million grant to Huntsman Cancer Institute at the University of Utah, and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope. [Huntsman Cancer Institute at the University of Utah] Press Release

Wistar Receives Grant from the Jayne Koskinas Ted Giovanis Foundation for Health and Policy to Support the Breast Cancer Research Consortium

The new award furthers the multidisciplinary research projects of two Wistar scientists, Frank J. Rauscher, III, Ph.D., the principal investigator of the award, and Qing Chen, M.D., Ph.D., whose integrated research targets breast cancer and specifically how cancer cells migrate from the primary tumor to form an often-deadly metastasis. [The Wistar Institute of Anatomy and Biology] Press Release

Chipscreen Biosciences Announces that a Pivotal Phase III Clinical Trial of Chidamide in Combination with Exemestane in Patients with Breast Cancer Reached Primary Endpoint

Shenzhen Chipscreen Biosciences Co., Ltd. has been informed that the company’s lead innovative product Epidaza^®, an oral subtype-selective histone deacetylase inhibitor, in combination with exemestane reached primary endpoint in a pivotal Phase III clinical trial. [Shenzhen Chipscreen Biosciences Co., Ltd. (PR Newswire Association LLC.)] Press Release

Celltrion Completes Resubmission for Biosimilar Candidate to FDA for Review

Celltrion has made a resubmission to the FDA to obtain its marketing approval for CT-P10, a proposed mAb biosimilar to Rituxan^®. Additionally, Celltrion plans on making a resubmission for the approval of CT-P6, a proposed biosimilar to Herceptin^® in June. [Celltrion Inc. (Business Wire, Inc.)] Press Release

After Brexit, Can British Science Have Its Cake and Eat It, Too?

Nearly two years after Britons voted to leave the European Union, Brexit’s impact on European science is finally coming into focus. Prime Minister Theresa May announced that the United Kingdom wants to take part in the next EU research-funding program, set to be worth almost €100 billion (US$116 billion). [Nature News] Editorial

Who Gets Credit for CRISPR? Prestigious Award Singles Out Three, and Leaves Out a Notable Scientist

One of the world’s richest science awards, given only in alternate years, will go to three discoverers of the CRISPR-Cas9 genome-editing tool, the Norwegian Academy of Science and Letters announced. Emmanuelle Charpentier of the Max Planck Institute for Infection Biology, Jennifer Doudna of the University of California, Berkeley, and Virginijus Šikšnys of Vilnius University will each receive a gold medal and share the $1 million that comes with the Kavli Prize in nanoscience. [STAT News] Editorial

Europe’s Science Spending Set for Another Big Boost

On 7 June, the European Commission will lay out detailed plans for one of the biggest single research programs on the planet. Called Horizon Europe, the program could be worth €97.6 billion between 2021 and 2027, up from about €77 billion for the current seven-year program, Horizon 2020. Its influence, however, will go beyond size. [ScienceInsider] Editorial

Max Planck Scientists Criticize Handling of Animal-Rights Charges against Leading Neuroscientist

Scientists at one of Germany’s leading neuroscience institutes say that their employer, the Max Planck Society, is failing in its responsibility to defend the institute’s scientists against efforts by animal-rights activists to disrupt research. [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 Research Associate – Breast Cancer (Howard University)

NEW Postdoctoral Fellow – Breast & Ovarian Cancer Genomics (University of Texas Health Science Center at Houston)

NEW Cancer Scientists – Breast Cancer Research (Qatar Biomedical Research Institute)

Postdoctoral Position – Ovarian and Breast Cancer Research (Indiana University School of Medicine)

Postdoctoral Position – Breast Cancer Research (Northwestern University)

Postdoctoral Posion – Basic & Translational Breast Cancer Research (Northwestern University)

Researcher Positions – Genome Directed Cancer Therapy (University of Bergen)

Postdoctoral Position – Genome Directed Cancer Therapy (University of Bergen)

Postdoctoral Positions – Translational Bioinformatics or Molecular Cancer Biology (University of Pittsburgh Cancer Institute)

Postdoctoral Research Fellow – Translational Mitochondrial Research (Fred Hutch Cancer Research Center)

Postdoctoral Position – Breast Cancer Research (Rutgers Cancer Institute of New Jersey)

Graduate Student – Breast and Colorectal Cancer (Dalhousie University)

Postdoctoral Fellows – Breast Cancer Stem Cell Research (New York University School of Medicine)

Postdoctoral Fellow or Research Scientist – Breast Cancer Research (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellowship – Cancer Research (Mass General Hospital/Harvard Medical School)

Postdoctoral Fellow – Breast Cancer Research (Northwestern University)

Postdoctoral Researcher – Breast Cancer (Baylor College of Medicine)

Senior Research Technician – Breast Cancer (Baylor College of Medicine)

Research Technician – Breast Cancer (Baylor College of Medicine)

Postdoctoral Fellow – Cancer Research (Indiana Uniersity School of Medicine)

Postdoctoral Researcher – Breast Cancer (UT Southwestern Medical Center)

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