Mammary Cell News Volume 9.37 | Sep 21 2017

TOP STORY

BRCA2 Suppresses Replication Stress-Induced Mitotic and G1 Abnormalities through Homologous Recombination

Researchers generated BRCA2 conditional non-transformed human mammary epithelial cell lines using CRISPR-Cas9. Cells are inviable upon BRCA2 loss, which leads to replication stress associated with under replication, causing mitotic abnormalities, 53BP1 nuclear body formation in the ensuing G1 phase, and G1 arrest. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Coactosin-Like Protein CLP/Cotl1 Suppresses Breast Cancer Growth through Activation of IL-24/PERP and Inhibition of Non-Canonical TGFβ Signaling

Scientists showed that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. [Oncogene] Abstract

EZH2 Contributes to the Response to PARP Inhibitors through Its PARP-Mediated Poly-ADP Ribosylation in Breast Cancer

Investigators showed enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributed to poly ADP-ribose polymerase (PARP) inhibitors sensitivity in breast cancer cells. [Oncogene] Abstract

Small-Molecule RL71-Triggered Excessive Autophagic Cell Death as a Potential Therapeutic Strategy in Triple-Negative Breast Cancer

The authors revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 exhibited potent anti-cancer activity on all triple-negative breast cancer (TNBC) cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca²⁺ from the endoplasmic reticulum into the cytosol by inhibiting SERCA2 activity. [Cell Death Dis] Full Article

RORα2 Requires LSD1 to Enhance Tumor Progression in Breast Cancer

Researchers generated retinoic acid-related orphan receptor α (RORα2)-specific antibody and characterized the role of RORα2 in promoting tumor progression in breast cancer. Intriguingly, RORα2 and lysine specific demethylase 1 (LSD1) protein levels are dramatically elevated in human breast cancer specimens compared to normal counterparts. [Sci Rep] Full Article

MPZL1 Forms a Signaling Complex with GRB2 Adaptor and PTPN11 Phosphatase in HER2-Positive Breast Cancer Cells

Scientists performed GRB2 affinity purification combined with mass spectrometry analysis of associated proteins in a HER2⁺ breast cancer model to delineate GRB2-nucleated protein interaction networks. They report the identification of the transmembrane protein MPZL1 as a new GRB2-associated protein. [Sci Rep] Full Article

G0S2 Represses PI3K/mTOR Signaling and Increases Sensitivity to PI3K/mTOR Pathway Inhibitors in Breast Cancer

In order to determine potential mechanisms of G0S2 anti-oncogenic activity, they performed genome-wide expression analysis that revealed an enrichment of gene signatures related to PI3K/mTOR pathway activation in G0S2 null cells as compared to G0S2 wild-type cells. [Cell Cycle] Abstract

Early Exposure to a High Fat/High Sugar Diet Increases the Mammary Stem Cell Compartment and Mammary Tumor Risk in Female Mice

Dimethylbenz[a]anthracene-induced carcinogenesis revealed that animals born to a mother fed a high fat/high sugar (HF/HS) gestation diet, nursed by a mother on a mildly diet-restricted, low fat/low sugar diet (DR) and weaned onto a HF/HS diet (HF/DR/HF) had the highest mammary tumor incidence, while HF/HF/DR had the lowest tumor incidence. [Cancer Prev Res (Phila)] Abstract

Tartrate-Resistant Acid Phosphatase (TRAP/ACP5) Promotes Metastasis-Related Properties via TGFβ2/TβR and CD44 in MDA-MB-231 Breast Cancer Cells

MDA-MB-231 breast cancer cells with different tartrate-resistant acid phosphatase (TRAP) expression levels were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes. [BMC Cancer] Full Article

Hsp90α Mediates BMI1 Expression in Breast Cancer Stem/Progenitor Cells through Facilitating Nuclear Translocation of c-Myc and EZH2

Researchers demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an inhibitor of Hsp90, could suppress the self-renewal of breast cancer stem cells by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. [Int J Mol Sci] Full Article | Graphical Abstract

Obesity and Breast Cancer – Role of Estrogens and the Molecular Underpinnings of Aromatase Regulation in Breast Adipose Tissue

The authors describe how obesity-related factors can affect the risk of hormone-dependent breast cancer, highlighting the different molecular mechanisms and metabolic pathways involved in aromatase regulation, estrogen production and breast malignancy in the context of obesity. [Mol Cell Endocrinol] Abstract

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STEMCELL Technologies Signs Exclusive License with Propagenix to Commercialize EpiX™, an Innovation Empowering Epithelial Cell Biology and Cell Therapy

STEMCELL Technologies has signed an exclusive license with Propagenix to commercialize its patented EpiX™ technology, a novel and revolutionary cell culture medium that enables unprecedented expansion of tissue-resident epithelial stem cells without any genetic manipulation. [STEMCELL Technologies Inc.] Press Release

£2 Million Award for Cancer Researcher

A University of Dundee scientist has been awarded £2 million to explore the role that one of the most fundamental processes in cell biology plays in cancer. Professor Karim Labib will receive the grant from Cancer Research UK to study mechanisms that preserve genome integrity during the final stages of chromosome replication in animal cells. [University of Dundee] Press Release

Oncolytics Biotech^® Announces Successful End-of-Phase II Meeting with FDA for REOLYSIN^® in Metastatic Breast Cancer

Oncolytics Biotech^® Inc. announced a successful End-of-Phase II meeting with the FDA for REOLYSIN in combination with paclitaxel, for the treatment of hormone receptor positive, HER2 receptor negative (HR⁺/HER2^–) metastatic breast cancer patients. [Oncolytics Biotech Inc.] Press Release

Publishers Go After Networking Site for Illicit Sharing of Journal Papers

A major scientific publishing group is taking aim at a social networking site for allowing researchers to illegally post copies of their journal papers. The International Association of Scientific, Technical, and Medical Publishers in Oxford, U.K., and The Hague, the Netherlands, has written to ResearchGate, a networking website for researchers, to express concerns over its article-sharing practices. [ScienceInsider] Editorial

They Got Hundreds of Thousands to Rally. Where Does the March for Science Go from Here?

The hundreds of thousands of people who rallied on the National Mall and in cities worldwide for the March for Science came to be noticed. But as two dozen of them met in New York the following month for a debrief, they faced an obvious reality: A grass-roots organization that was quickly formed to plan a singular event was not, at least immediately, equipped for far-reaching and long-term science advocacy. [STAT News] Editorial

U.S. House Approves 2018 Spending Bills, but Process Far from Finished

The U.S. House of Representatives took a major step toward setting federal science budgets for the 2018 fiscal year. But Congress is still far from the finish line, and final spending levels aren’t likely to be finalized until late this year at the earliest. [ScienceInsider] Editorial

NEW Keystone Symposia: Precision Medicine in Cancer
May 6-10, 2018
Stockholm, Sweden

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NEW Higher Scientific Officer – Breast Cancer Research (Institute of Cancer Research)

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

Postdoctoral Opportunities – Cancer Research (Albert Einstein College of Medicine in New York)

Research Associate – Triple Negative Breast Cancer (University of Cambridge)

Faculty Positions – Basic and Translational Cancer Research (Texas Tech University Health Science Center El Paso)

Postdoctoral Position – Mammary Gland Stem Cells (Université Libre de Bruxelles)

Postdoctoral Position – Mammary Tumors (Cancer Research UK Beatson Institute)

Clinician Investigator – Breast Cancer Research (Mayo Clinic)

Research Fellows – Cancer Research (National University of Singapore)

Multiple Positions – Cancer Research (National University of Singapore)

Postdoctoral Position – Breast Cancer Research (Massachusetts General Hospital Cancer Center)

PhD Student – Breast Cancer Biology (VIB-KULeuven Center for Cancer Biology)

Associate Medical Director/Medical Director – Breast Cancer (Genentech, Inc.)

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