Mammary Cell News Volume 10.24 | Jun 21 2018

TOP STORY

Mammary Molecular Portraits Reveal Lineage-Specific Features and Progenitor Cell Vulnerabilities

Researchers built a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. They defined systems-level relationships between chromatin–DNA–RNA-protein states, identified lineage-specific DNA methylation of transcription factor binding sites, and pinpointed proteins underlying progesterone responsiveness. [J Cell Biol] Full Article | Press Release

(Ranked by impact factor of the journal)

Inhibition of Epithelial Cell Migration and Src/FAK Signaling by SIRT3

The authors found that, although mitochondria are present at the leading edge of migrating cells, SIRT3 expression was down-regulated during migration, resulting in elevated reactive oxygen species (ROS) levels. This SIRT3-mediated control of ROS repressed Src oxidation and attenuated focal adhesion kinase (FAK) activation. [Proc Natl Acad Sci USA] Full Article

Chemotherapy Sensitizes Therapy-Resistant Cells to Mild Hyperthermia by Suppressing Heat Shock Protein 27 Expression in Triple Negative Breast Cancer

MDA-MB-231 and SUM159 triple-negative breast cancer cells treated with docetaxel micelles (mDTX)-loaded gold nanoparticle-coated porous silicon microparticle and mild hyperthermia displayed significantly reduced efficiencies in mammosphere formation than those treated with mDTX alone or mild hyperthermia alone. Combination treatment also completely inhibited SUM159 orthotopic tumor growth and 4T1 tumor metastasis. [Clin Cancer Res] Abstract | Full Article

Identification of Highly Penetrant Rb-Related Synthetic Lethal Interactions in Triple Negative Breast Cancer

Researchers identified candidate synthetic lethal (SL) interactions associated with RB1 defects in triple-negative breast cancer (TNBC). Small-molecule inhibition of SCF^SKP elicited an increase in p27^Kip levels, providing a mechanistic rationale for RB1 SL. Transcript expression of SKP2, a SCF^SKP component, was elevated in RB1-defective TNBCs, suggesting that in these tumors, SKP2 activity might buffer the effects of RB1 dysfunction. [Oncogene] Full Article

G1P3 (IFI6), a Mitochondrial Localised Antiapoptotic Protein, Promotes Metastatic Potential of Breast Cancer Cells through mtROS

Consequent to its localization on inner-mitochondrial membrane, mtROS were higher in G1P3-expressing cells. G1P3-overexpressing cells migrated and invaded faster than the vector controls with increased number of filopodia and F-actin bundles. mtROS suppression with H₂O₂ scavengers and mitochondrial-specific antioxidants significantly decreased migratory structures and reversed G1P3-induced migration and invasion. [Br J Cancer] Abstract

Expression of ID4 Protein in Breast Cancer Cells Induces Reprogramming of Tumor-Associated Macrophages

In vitro and in vivo migration assays demonstrated that expression of inhibitor of differentiation 4 (ID4) in breast cancer cells stimulates macrophage motility. At the molecular level, ID4 protein expression in breast cancer cells controlled, through paracrine signaling, the activation of an angiogenic program in macrophages. [Breast Cancer Res] Full Article

SNAI2 Upregulation Is Associated with an Aggressive Phenotype in Fulvestrant-Resistant Breast Cancer Cells and Is an Indicator of Poor Response to Endocrine Therapy in Estrogen Receptor-Positive Metastatic Breast Cancer

SNAI2 was found to be significantly upregulated in all endocrine-resistant cells compared to parental cell lines, while no changes were observed in the expression of other epithelial-mesenchymal transition-associated transcription factors. SNAI2 knockdown with specific small interfering RNA converted the mesenchymal-like fulvestrant-resistant cells into an epithelial-like phenotype and reduced cell motility. [Breast Cancer Res] Full Article

Label-Free Detection of Hypoxia-Induced Extracellular Vesicle Secretion from MCF-7 Cells

Scientists presented a label-free electrochemical sensor to measure extracellular vesicles (EVs) secretion levels of hypoxic and normoxic MCF-7 cells. The sensor design included two consecutive steps; Au electrode surface functionalization for anti-CD81 antibody and EVs capture. The label-free detection of EVs was done via differential pulse voltammetry and electrochemical impedance spectroscopy. [Sci Rep] Full Article

Neutrophil TLR4 and PKR Are Targets of Breast Cancer Cell Glycosaminoglycans and Effectors of Glycosaminoglycan-Induced APRIL Secretion

While stimulation of the RNA-activated protein kinase (PKR) was sufficient to induce neutrophil a proliferation-inducing ligand (APRIL) secretion, both PKR and the toll-like receptor 4 (TLR4) were required for breast cancer cell glycosaminoglycan-induced secretion as separate and specific inhibition of TLR4 or PKR completely prevented the process, suggesting that breast cancer cell glycosaminoglycans targeted neutrophil TLR4 and PKR to trigger APRIL secretion. [Oncogenesis] Full Article

Oncoprotein HBXIP Induces PKM2 via Transcription Factor E2F1 to Promote Cell Proliferation in ER-Positive Breast Cancer

In estrogen receptor (ER) positive breast cancer cells, hepatitis B X-interacting protein (HBXIP) upregulated pyruvate kinase muscle isozyme M2 (PKM2) expression at mRNA and protein levels in a dose-dependent manner, as well as increased the activity of the PKM promoter. HBXIP stimulated the PKM promoter through binding to the −779/−579 promoter region involving co-activation of E2F transcription factor 1 (E2F1). [Acta Pharmacol Sin] Abstract

miR-182 Regulates Trastuzumab Resistance by Targeting MET in Breast Cancer Cells

Investigators revealed that overexpression of miR-182 reduced trastuzumab resistance in trastuzumab-resistant cells due in part to MET/PI3K/AKT/mTOR signaling pathway inactivation. Furthermore, miR-182 also sensitized SKBR3/TR cells to trastuzumab in vivo. [Cancer Gene Ther] Abstract

Statins – a Role in Breast Cancer Therapy?

A considerable body of preclinical, epidemiologic, and clinical evidence shows that statins impair proliferation of breast cancer cells and reduce the risk of breast cancer recurrence. Potential mechanisms for this effect have been explored in laboratory models, but remain poorly understood and require further investigation. [J Intern Med] Abstract | Full Article

MicroRNAs in Regulation of Triple-Negative Breast Cancer Progression

The authors provide a comprehensive review of the existing data on microRNAs in triple-negative breast cancer, their molecular targets, a putative role in invasive progression with a particular emphasis on the epithelial-to-mesenchymal transition and acquisition of stem-cell properties, regarded both as prerequisites for metastasis, and significance for therapy. [J Cancer Res Clin Oncol] Full Article

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

MetaStat Presents Positive Data Showing Inhibition of the MENA-Pathway Reduces Cancer Cell Dissemination and Paclitaxel Resistance in Aggressive Cancer

MetaStat, Inc., presented positive results from preclinical studies showing treatment with MAPKAPK2 kinase inhibitors reverse MENA-driven aggressive tumor cell phenotypes and significantly reduce metastasis. [Press release from MetaStat, Inc. discussing research presented at the Cancer Dormancy and Residual Disease Meeting of the American Association for Cancer Research (AACR), Montreal] Press Release

Natera and Institut Jules Bordet Announce Collaboration in Neoadjuvant Breast Cancer

Natera, Inc., announced a research collaboration with the Institut Jules Bordet, using the company’s Signatera^™ research-use-only circulating tumor DNA assay to evaluate molecular response and minimal residual disease in women with early stage breast cancer. [Natera, Inc.] Press Release

Champions Oncology Partners with Puma Technology and NASBP Foundation on Metastatic Breast and Colon Cancer Co-Clinical PDX Studies

Champions Oncology, Inc., announced that they have partnered with NSABP Foundation, Inc.and Puma Technology, Inc. to develop patient derived xenograft (PDX) models in two multi-center co-clinical PDX trials. The first trial, NSABP FB10 is a Phase II study evaluating the combination of trastuzumab emtansine with neratinib in women with metastatic HER2-positive breast cancer and is currently enrolling patients. [Champion Oncology, Inc.] Press Release

Hundreds of U.S. Scientists Urge More Transparency in Animal Research

Breaking with a history of reticence, nearly 600 scientists, students, and lab animal workers published a letter in USA Today that calls on U.S. research institutions to “embrace openness” about their animal research. [ScienceInsider] Editorial

U.S. Legislators Back Larger Facilities Budget for NSF

The National Science Foundation (NSF) in Alexandria, Virginia, is in line for a budget increase of 4% to 5% next year. That assessment is based on bills approved recently by the spending committees in both chambers of Congress. Lawmakers have also signaled support for growing the account that NSF uses to build major new scientific facilities. [ScienceInsider] Editorial

Why the Medical Research Grant System Could Be Costing Us Great Ideas

The medical research grant system in the United States, run through the National Institutes of Health, is intended to fund work that spurs innovation and fosters research careers. In many ways, it may be failing. [The New York Times] Editorial

House Bill Gives NIH a 3% Boost in 2019, to $38.3 Billion

A draft bill released by a House of Representatives spending panel would give the National Institutes of Health (NIH) in Bethesda, Maryland, a $1.25 billion raise in 2019, to $38.3 billion. That is 3% more than this year’s level and $4.1 billion more than President Donald Trump’s administration had requested. [ScienceInsider] Editorial

UCal and Partners Win U.S. Patent Related to CRISPR-Cas9

The Regents of the University of California (UCal), the University of Vienna, and Emmanuelle Charpentier, Ph.D., of the Max-Planck Institute in Berlin, have been granted a U.S. patent for intellectual property related to CRISPR-Cas9 genome-editing technology. [Genetic Engineering & Biotechnology News] Editorial

NEW 2018 Till & McCulloch Meetings (TMM2018)
November 12-14, 2018
Ottawa, Ontario, Canada

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

NEW Cancer Faculty Investigators – Basic & Translational Cancer Research (The University of Alabama)

NEW Postdoctoral Fellow – Molecular Mechanisms of Breast & Colon Cancers (Dalhousie University)

Post-doctoral Fellow – Ovarian and Breast Cancers (John Hopkins University)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University Feinberg School of Medicine)

Postdoctoral Research Associate – Breast Cancer (Howard University)

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

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)

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

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

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

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