Mammary Cell News Volume 8.17 | May 5 2016

Combined Inhibition of DNMT and HDAC Blocks the Tumorigenicity of Cancer Stem-Like Cells and Attenuates Mammary Tumor Growth
Scientists used the MMTV-Neu-Tg mouse mammary tumor model to identify potential new strategies for eliminating cancer stem cells. They found that both luminal progenitor and basal stem cells are susceptible to genetic and epigenetic modifications, which facilitate oncogenic transformation and tumorigenic potential. [Cancer Res] Abstract | Press Release

The Mitochondrial Calcium Uniporter Regulates Breast Cancer Progression via HIF-1α
Investigators showed that expression of the mitochondrial calcium uniporter, the selective channel responsible for mitochondrial Ca²⁺ uptake, correlates with tumor size and lymph node infiltration, suggesting that mitochondrial Ca²⁺ uptake might be instrumental for tumor growth and metastatic formation. [EMBO Mol Med] Full Article | Graphical Abstract

Tumor Suppressor SET9 Guides the Epigenetic Plasticity of Breast Cancer Cells and Serves as an Early-Stage Biomarker for Predicting Metastasis
The authors identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. [Oncogene] Abstract

Elevated Expression of Chemokine C-C Ligand 2 in Stroma Is Associated with Recurrent Basal-Like Breast Cancers
Investigators employed a software-based approach to evaluate the prognostic significance of chemokine C-C ligand 2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1, a mesenchymal marker. [Mod Pathol] Abstract

The Calcium Pump Plasma Membrane Ca2⁺-ATPase 2 (PMCA2) Regulates Breast Cancer Cell Proliferation and Sensitivity to Doxorubicin
Scientists showed that PMCA2 is expressed in human epithelia undergoing lactational remodeling and also report strong PMCA2 staining on apical membranes of luminal epithelia in approximately 9% of human breast cancers they assessed. [Sci Rep] Full Article

Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines that Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase
Compounds were derived from the promiscuous kinase inhibitor PP1 to search for analogs that could potentially target a broad spectrum of kinases involved in cancer. Phenotypic screening against MCF7 mammary adenocarcinoma cells generated target-agnostic structure-activity relationships that biased subsequent designs toward breast cancer treatment rather than to a particular target. [J Med Chem] Abstract

GR and ER Co-Activation Alters the Expression of Differentiation Genes and Associates with Improved ER⁺ Breast Cancer Outcome
To understand the mechanism by which glucocorticoid receptor (GR) expression is associated with a better ER⁺ breast cancer (BC) outcome, the global effect of GR-mediated transcriptional activation in ER⁺ BC cells was studied. Analysis of GR chromatin immunoprecipitation followed by high-throughput sequencing in ER⁺/GR⁺ MCF-7 cells revealed that upon co-activation of GR and ER, GR chromatin association became enriched at proximal promoter regions. [Mol Cancer Res] Abstract

Testing Chemotherapy Efficacy in HER2 Negative Breast Cancer Using Patient-Derived Spheroids
A predictive test was developed using patient-derived spheroids to identify the most effective therapy for patients with HER2 negative breast cancer of all stages, for clinically relevant subgroups, as well as individual patients. [J Transl Med] Full Article

Silibinin and Indocyanine Green-Loaded Nanoparticles Inhibit the Growth and Metastasis of Mammalian Breast Cancer Cells In Vitro
Researchers designed a new nanosized drug delivery system loaded with an anti-metastatic drug silibinin and a photothermal agent indocyanine green, and investigated its effects on the growth and metastasis of breast cancer cells in vitro. [Acta Pharmacol Sin] Abstract

CLINICAL RESEARCH

Pembrolizumab in Patients with Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Researchers assessed the safety and antitumor activity of the programmed cell death protein 1 inhibitor pembrolizumab in patients with advanced triple-negative breast cancer. [J Clin Oncol] Abstract

In Vivo Imaging of Eribulin-Induced Reoxygenation in Advanced Breast Cancer Patients: A Comparison to Bevacizumab
Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To compare the anti-angiogenic activity of eribulin to that of bevacizumab, the authors compared tumor vessel remodeling and reoxygenation between the two agents. [Br J Cancer] Abstract

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The Pershing Square Sohn Cancer Research Alliance Awards Funding to Seven New York City-Based Cancer Research Scientists
The Pershing Square Sohn Cancer Research Alliance announced seven winners of the third annual Pershing Square Sohn Prize for Young Investigators in Cancer Research. Each will receive $200,000 in funding per year for up to three years to enable them to continue to pursue explorative and high-risk/high-reward research. [The Pershing Square Foundation (BusinessWire)] Press Release

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NEW Research Associate – Various Medical Disciplines (Jinan University)

NEW Part-Time Researcher – Molecular Markers in Breast Cancer (University of Bergen)

Research Technologist – Mammary and Prostate Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – RNA Splicing in Breast Cancer (Memorial Sloan Kettering Cancer Center)

Scientist – Cancer Research (Institute of Clinical Physiology)

Postdoctoral Fellow – Metastatic Reactivation of Cancer (MD Anderson Cancer Center)

Faculty Position – Cancer Immunology (University of New Mexico)

Faculty Position – Cancer Research (Eppley Institute for Research in Cancer)

Postdoctoral Fellow – Breast Cancer (Northwestern University)

Faculty Position – Tumor Immunology (John Wayne Cancer Institute at Providence Saint John’s Health Center)

Postdoctoral Fellow – Noncoding RNAs in Breast Cancer (University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Breast and Ovarian Cancer (Johns Hopkins University School of Medicine)

Postdoctoral Fellowship – Platelets in Metastatic Breast and Colon Cancer (Université de Strasbourg)

Manager – Medical and Breast Imaging (Fred Hutchinson Cancer Research Center)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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