Mammary Cell News Volume 11.24 | Jun 27 2019

TOP STORY

Inadequate DNA Damage Repair Promotes Mammary Transdifferentiation, Leading to BRCA1 Breast Cancer

In mammary epithelial cells (MECs), BRCA1 interacted with multiple proteins, including NUMB and HES1, to form complexes that participated in interstrand crosslink DNA repair and MEC differentiation control. [Cell] Abstract | Graphical Abstract

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The VEGF Receptor Neuropilin 2 Promotes Homologous Recombination by Stimulating YAP/TAZ-Mediated Rad51 Expression

Investigators discovered that vascular endothelial growth factor (VEGF)-NRP2-YAP/TAZ signaling contributed to the resistance of triple-negative breast cancer cells to cisplatin and that Rad51 rescued the defects in DNA repair upon inhibition of either VEGF-NRP2 or YAP/TAZ. [Proc Natl Acad Sci USA] Abstract

Mesenchymal Stem/Stromal Cell Engulfment Reveals Metastatic Advantage in Breast Cancer

Using flow cytometry and a microfluidic single-cell paring and retrieval platform, the authors showed that mesenchymal stem/stromal cell engulfment capacity was associated with breast cancer cell metastatic potential and generated cells with mesenchymal-like, invasion, and stem cell traits. [Cell Rep] Full Article | Graphical Abstract

Knockdown of TM9SF4 Boosts ER Stress to Trigger Cell Death of Chemoresistant Breast Cancer Cells

Scientists found that expression of TM9SF4 proteins was much higher in adriamycin (ADM)-resistant breast cancer cells MCF-7/ADM than in its parental line wild-type breast cancer cells MCF-7/WT. [Oncogene] Abstract

3D Bioprinted Mammary Organoids and Tumoroids in Human Mammary Derived ECM Hydrogels

Researchers describe a novel mammary-specific culture protocol that combined a self-gelling hydrogel comprised solely of extracellular matrix (ECM) from decellularized rat or human breast tissue with the use of a previously described 3D bioprinting platform. [Acta Biomater] Abstract | Graphical Abstract

Notch2 Pathway Mediates Breast Cancer Cellular Dormancy and Mobilization in Bone and Contributes to Hematopoietic Stem Cell Mimicry

Notch2 signal implication was demonstrated by immunophenotyping the endosteal niche-associated cancer cells and upon co-culture with sorted endosteal niche cells, which inhibited breast cancer cell proliferation in a Notch2-dependent manner. [Br J Cancer] Full Article

LINC01355 Suppresses Breast Cancer Growth through FOXO3-Mediated Transcriptional Repression of CCND1

LINC01355 were downregulated in breast cancer cells relative to non-malignant breast epithelial cells. Overexpression of LINC01355 significantly inhibited proliferation, colony formation, and tumorigenesis of breast cancer cells. [Cell Death Dis] Full Article

The Beneficial Androgenic Action of Steroidal Aromatase Inactivators in Estrogen-Dependent Breast Cancer after Failure of Nonsteroidal Drugs

Researchers investigated the influence of Formestane and Exemestane and of their major androgenic metabolites 4-hydroxytestosterone and 17-hydroexemestane on the proliferation of MCF-7 cells and ZR-75-1 cells. [Cell Death Dis] Full Article

EIF2A Promotes Cell Survival during Paclitaxel Treatment In Vitro and In Vivo

Scientists showed that paclitaxel, the major chemotherapy drug for breast cancer, induced integrated stress response and phosphorylated ser51 residue of EIF2S1 by EIF2AK3 and EIF2AK4. When exposed to paclitaxel, cancer cells activated the EIF2AK3/EIF2AK4‐pEIF2S1‐ATF4 axis and maintained redox homoeostasis by inducing expression of the major antioxidant enzymes HMOX1, SHMT2 and SLC7A11. [J Cell Mol Med] Full Article

Honokiol Inhibits Breast Cancer Cell Metastasis by Blocking EMT through Modulation of Snail/Slug Protein Translation

Investigators showed that honokiol dose-dependently inhibited the viability of human mammary epithelial tumor cell lines MCF7, MDA-MB-231, and mouse mammary tumor cell line 4T1. [Acta Pharmacol Sin] Abstract

Ascorbate Promotes the Cellular Accumulation of Doxorubicin and Reverses the Multidrug Resistance in Breast Cancer Cells by Inducing ROS-Dependent ATP Depletion

Scientists found that combined administration of ascorbate improved the sensitivity of both MCF-7 and doxorubicin (Dox)-resistant MCF-7/Adr cells to Dox in vitro and in vivo by a reactive oxygen species (ROS)-dependent mechanism. [Free Radic Res] Abstract

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The Emerging Role of Circular RNAs in Breast Cancer

The authors concentrated on biogenesis and function of circular RNAs, summarized their implications in breast cancer (BCa) and discussed their potential as diagnostic and therapeutic targets for BCa. [Biosci Rep] Full Article

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Immutep Completes Patient Enrollment of the AIPAC Phase IIb Clinical Trial in Metastatic Breast Cancer

Immutep Limited announced that it has completed patient enrollment of the Phase IIb Active Immunotherapy PAClitaxel (AIPAC) clinical trial in HER2-negative/hormone receptor positive metastatic breast cancer. [Immutep Limited] Press Release

ERYTECH Announces Enrollment of First Patient in Phase II Clinical Trial Evaluating Eryaspase in TNBC

ERYTECH Pharma announced that the first patient has been enrolled in its Phase II clinical trial, named TRYbeCA2, evaluating its lead product candidate eryaspase for the treatment of first line triple negative breast cancer (TNBC). [ERYTECH Pharma] Press Release

Zenith Epigenetics Announces Dosing of First Patient in Triple Negative Breast Cancer Trial with Pfizer

Zenith Epigenetics Ltd. announced that it has dosed the first patient in a Phase Ib/II clinical trial undertaken in collaboration with Pfizer Inc. [Zenith Epigenetics Ltd.] Press Release

Arvinas Receives Authorization to Proceed for ARV-471, a PROTAC^® Protein Degrader to Treat Patients with Locally Advanced or Metastatic ER⁺/HER2^– Breast Cancer

Arvinas, Inc. announced that the FDA has cleared the company’s Investigational New Drug application for ARV-471, an oral estrogen receptor (ER) PROTAC^® protein degrader, designed to selectively target ER for the treatment of patients with locally advanced or metastatic ER positive/HER2 negative breast cancer. [Arvinas, Inc.] Press Release

Minerva Biotechnologies Announces FDA Acceptance of IND Application for HuMNC2-CAR44 T Cells to Treat Metastatic Breast Cancer

Minerva Biotechnologies announced that the FDA has approved their Investigational New Drug (IND) application to conduct clinical trials with huMNC2-CAR44, an autologous CAR T cell therapy for solid tumors. [Minerva Biotechnologies] Press Release

European Commission Approves TALZENNA^® (Talazoparib) for Patients with Inherited (Germline) BRCA-Mutated Locally Advanced or Metastatic Breast Cancer

Pfizer Inc. announced that the European Commission approved TALZENNA^®, an oral poly (ADP-ribose) polymerase inhibitor, as monotherapy for the treatment of adult patients with germline breast cancer susceptibility gene 1/2-mutations, who have human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. [Pfizer Inc.] Press Release

NIH Probe of Foreign Ties Has Led to Undisclosed Firings—and Refunds from Institutions

An aggressive effort by the National Institutes of Health (NIH) to enforce rules requiring its grantees to report foreign ties is still gathering steam. But it has already had a major impact on the US biomedical research community. A senior NIH official tells ScienceInsider that universities have fired more scientists—and refunded more grant money—as a result of the effort than has been publicly known. [ScienceInsider] Editorial

Discrimination Drives LGBT+ Scientists to Think About Quitting

Nearly one-third of physical scientists from sexual and gender minorities in the United Kingdom have considered leaving their jobs because of their workplace climate, suggests a survey. And 18% who are lesbian, gay, bisexual, transgender or from other sexual and gender minorities (LGBT+) said they had experienced harassment, bullying or exclusionary behavior in the workplace. [Nature News] Editorial

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October 1, 2019
London, United Kingdom

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NEW Postdoctoral Fellowship – Redox Biology of Lung and Breast Cancer (Washington University School of Medicine)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

Canada Research Chair – Precision and Molecular Oncology (University of Calgary)

PhD Studentship – Molecular Mechanisms of Breast and Colorectal Cancers (Dalhousie University)

Postdoctoral Fellowship – Molecular Mechanisms of Breast and Colorectal Cancers (Dalhousie University)

Senior Global Medical Director – Breast Cancer (F.Hoffmann-La Roche)

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

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

Postdoctoral Fellows – Bioinformatics (IRCCS European Institute of Oncology)

Postdoctoral Associate – Cancer Immunology (The Jackson Laboratory)

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