Mammary Cell News Volume 10.30 | Aug 2 2018

TOP STORY

The Actin Cytoskeletal Architecture of Estrogen Receptor Positive Breast Cancer Cells Suppresses Invasion

Researchers showed that estrogen suppresses invasion of estrogen receptor (ER)-positive breast cancer cells by increasing transcription of the Ena/VASP protein, EVL, which promoted the generation of suppressive cortical actin bundles that inhibited motility dynamics, and was crucial for the ER-mediated suppression of invasion in vitro and in vivo. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

CCL20 Triggered by Chemotherapy Hinders the Therapeutic Efficacy of Breast Cancer

NF-κB activation increased C-C motif chemokine ligand 20 (CCL20) expression, forming a positive feedback loop between NF-κB and CCL20 pathways, which provided sustained impetus for chemoresistance in breast cancer cells. [PLoS Biol] Full Article

Myoepithelial Cells Are a Dynamic Barrier to Epithelial Dissemination

Myoepithelial-specific Twist1 expression induced cell-autonomous myoepithelial cell escape. Luminal-specific Twist1 expression was rarely sufficient for escape. Scientists revealed that myoepithelial cells collectively restrained and reinternalized invading Twist1⁺ luminal cells. [J Cell Biol] Abstract | Press Release

The Interaction between Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 and HER2 Is Associated with Therapeutic Efficacy of Trastuzumab in Breast Cancer

Carcinoembryonic antigen-related cell adhesion molecule 6 knockdown decreased the inhibitory effects of trastuzumab in trastuzumab-sensitive BT-474 and HCC-1419, but not in trastuzumab-resistant MDA-MB-361 cells. [J Pathol] Abstract

Novel Hybrid Conjugates with Dual Suppression of Estrogenic and Inflammatory Activities Display Significantly Improved Potency against Breast Cancer

The authors developed a small library of novel oxabicycloheptene sulfonate-resveratrol (RES) hybrid compounds with dual inhibition activities targeting both the estrogen receptor α (ERα) and NF-κB by incorporating RES, a known inhibitor of NF-κB, into a privileged indirect antagonism structural motif of ER. [J Med Chem] Abstract

miR-205-5p Inhibition by Locked Nucleic Acids Impairs Metastatic Potential of Breast Cancer Cells

Investigators showed that miR-205-5p regulated tumorigenic properties of breast cancer cells, as well as epithelial to mesenchymal transition. Silencing this miRNA in breast cancer resulted in reduced tumor growth and metastatic spreading in mouse models. [Cell Death Dis] Full Article

Co-Inhibition of mTORC1, HDAC and ESR1α Retards the Growth of Triple-Negative Breast Cancer and Suppresses Cancer Stem Cells

The authors showed that fractionated cancer stem cells (CSCs) expressed higher levels of mTORC1 and HDAC than non-CSCs. As a result, co-inhibition of mTORC1, HDAC, and ESR1 was capable of reducing both bulk and CSC subpopulations as well as the conversion of fractionated non-CSC to CSCs in triple-negative breast cancer cells. [Cell Death Dis] Full Article

Long Non-Coding RNA SNHG14 Induces Trastuzumab Resistance of Breast Cancer via Regulating PABPC1 Expression through H3K27 Acetylation

Researchers revealed that overexpression of SNHG14 promoted cell proliferation, invasion and trastuzumab resistance, whereas knockdown of SNHG14 showed an opposite effect. PABPC1 gene was identified as a downstream target of SNHG14, and PABPC1 mediated the SNHG14-induced oncogenic effects. [J Cell Mol Med] Full Article

A Dual Role of miR-22 Modulated by RelA/p65 in Resensitizing Fulvestrant-Resistant Breast Cancer Cells to Fulvestrant by Targeting FOXP1 and HDAC4 and Constitutive Acetylation of p53 at Lys382

Scientists identified two NF-κB binding motifs in the miR-22 promoter that contributed to transcriptional repression of miR-22. Activation of RelA/p65, triggered by LPS, attenuated miR-22 expression, but this expression was restored by sc-514, a selective IKKβ inhibitor. [Oncogenesis] Full Article

Three-Dimensional Tissue Culture Model of Human Breast Cancer for the Evaluation of Multidrug Resistance

A more pathologically relevant, three-dimensional culture of human breast cancer cells was developed by seeding the adriamycin-resistant cells MCF-7R in silk-collagen scaffolds. Distinct growth profiles of MCF-7R and MCF-7 cells were observed when they were cultured in the scaffolds in comparison with those in the monolayer culture, including cell proliferation, cellular aggregate formation and expression of drug resistance-related genes/proteins. [J Tissue Eng Regen Med] Abstract

Combinational Proanthocyanidins and Resveratrol Synergistically Inhibit Human Breast Cancer Cells and Impact Epigenetic-Mediating Machinery

Researchers showed that treatments with grape seed proanthocyanidins and resveratrol in combination synergistically induced apoptosis in MDA-MB-231 cells by upregulating Bax expression and down-regulating Bcl-2 expression. [Int J Mol Sci] Full Article | Graphical Abstract

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CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest

The authors describe the less-appreciated effects of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors on cancer cells, and suggest ways by which they might be exploited to enhance the benefits of these agents for cancer patients. [Trends Cell Biol] Abstract

Breast Cancer Stem Cells: Features, Key Drivers and Treatment Options

The current view is that breast cancer is a stem cell disease characterized by the existence of cancer cells with stem-like features and tumor-initiating potential. Common therapies by chemotherapeutic drugs fail to eradicate these cells and rather increase the pool of cancer stem cells in tumors, an effect that may increase the likelyhood of recurrence. [Semin Cancer Biol] Abstract

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Pfizer Receives European Approval for Oncology Biosimilar, TRAZIMERA^™ (Trastuzumab)

Pfizer Inc. announced the European Commission has approved TRAZIMERA^™, a biosimilar to Herceptin^®, for the treatment of human epidermal growth factor (HER) overexpressing breast cancer and HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. [Pfizer Inc.] Press Release

Puma Biotechnology Files New Drug Submission for NERLYNX^® in Canada

Puma Biotechnology, Inc., announced that Health Canada has accepted for review the company’s New Drug Submission for the medicinal product NERLYNX^® for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer following adjuvant trastuzumab-based therapy. [Puma Biotechnology, Inc.] Press Release

Phase III Study of Subcutaneous Pertuzumab and Trastuzumab Initiated Using Halozyme’s ENHANZE^® Technology

Halozyme Therapeutics, Inc. announced that Genentech, a member of the Roche Group, has dosed the first patient in a Phase III study of a fixed-dose combination of pertuzumab and trastuzumab for subcutaneous administration using Halozyme’s proprietary ENHANZE^® drug-delivery technology in combination with chemotherapy. [Halozyme, Inc.] Press Release

Avelas Biosciences Initiates Period 2 of Phase II Study of AVB-620 in Women with Primary, Nonrecurrent Breast Cancer Undergoing Surgery

Avelas Biosciences, Inc., announced that the first patient has been dosed in Period 2 of its Phase II clinical trial of AVB-620 in women with primary, nonrecurrent breast cancer undergoing surgery. [Avelas Biosciences] Press Release

Brexit Preparedness: EMA to Further Temporarily Scale Back and Suspend Activities

The European Medicines Agency (EMA) will launch the next phase of its business continuity plan on 1 October 2018 at the latest. This will allow the Agency to safeguard core activities related to the evaluation and supervision of medicines, while it has to intensify its preparations for the physical move to Amsterdam in March 2019 and cope with significant staff loss. [European Medicines Agency] Press Release

Trump’s Pick to Head White House Science Office Gets Good Reviews

President Donald Trump announced that he intends to nominate meteorologist Kelvin Droegemeier, a university administrator and former vice-chair of the governing board of the U.S. National Science Foundation, to be director of the White House Office of Science and Technology Policy. [ScienceInsider] Editorial

Series of Ethical Stumbles Tests NIH’s Reliance on Private Sector for Research Funding

NIH officials told STAT the agency is completing a plan to ensure better ethical compliance and better delineate the actual process for private-sector collaboration. The officials said the plan will be presented to an advisory committee in December. [STAT News] Editorial

NEW Cancer Stem Cells: Impact on Treatment 2018
December 11-15, 2018
Seefeld, Austria

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NEW Postdoctoral Positions – Breast Cancer Research (UPMC Hillman Cancer Center)

NEW Cancer Faculty Investigators – Cancer Research (University of Alabama at Birmingham)

NEW Postdoctoral Research Fellow – Immuno/Oncology of Breast Cancer (Henry M. Jackson Foundation)

Research Assistant/Associate – Breast Cancer Therapeutics (King’s College London)

Research Assistant/Associate – Translational Breast Cancer Research (Icahn School of Medicine at Mount Sinai)

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

Postdoctoral Training Fellow – Breast Cancer Research (Institute of Cancer Research)

Postdoctoral Research Scientist – DNA Repair Assay, Breast Cancer (Columbia Center for Radiological Research)

Postdoctoral Position – Breast Cancer (University of Trento)

Instructor or Assistant Professor – Breast and Colon Cancer Metastasis Research (Louisiana State University Health Sciences Center)

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

Postdoctoral Research Associate – Breast Cancer (Howard University)

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

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