Mammary Cell News Volume 11.13 | Apr 11 2019

TOP STORY

Cortical Branched Actin Determines Cell Cycle Progression

Investigators report that branched actin networks from the cell cortex depended on ARPC1B-containing Arp2/3 complexes and that they were specifically monitored by type I coronins to control cell cycle progression in mammary epithelial cells. Cortical ARPC1B-dependent branched actin networks were regulated by the RAC1/WAVE/ARPIN pathway and drove lamellipodial protrusions. [Cell Res] Full Article

(Ranked by impact factor of the journal)

The miR-186-3p/EREG Axis Orchestrates Tamoxifen Resistance and Aerobic Glycolysis in Breast Cancer Cells

Researchers showed that EREG was a direct target of miR-186-3p and that downregulation of miR-186-3p by tamoxifen resulted in EREG upregulation in tamoxifen-resistant breast cancer cells. Systemic delivery of cholesterol-modified agomiR-186-3p to mice bearing tamoxifen-resistant breast tumors effectively attenuated both tumor growth and [¹⁸F]-fluoro-deoxyglucose uptake. [Oncogene] Full Article

LncRNA NORAD Is Repressed by the YAP Pathway and Suppresses Lung and Breast Cancer Metastasis by Sequestering S100P

Scientists showed that long noncoding RNA (lncRNA) NORAD was downregulated in lung and breast cancers, and that NORAD low expression in these cancer types was associated with lymph node metastasis and poor prognosis. NORAD was transcriptionally repressed by the Hippo pathway transducer YAP/TAZ-TEAD complex in conjunction with the action of NuRD complex. [Oncogene] Abstract

Carbon Nanotube-Delivered iC9 Suicide Gene Therapy for Killing Breast Cancer Cells in Vitro

Investigators aimed to induce a safe death to the MCF-7 human breast cancer cell line through gene therapy based on the iC9 suicide gene. To induce apoptosis to the MCF-7 cell line, the iC9 gene was transfected using pyridine-functionalized multi-walled carbon nanotubes. Then, to enhance chemotherapy, iC9 suicide gene therapy was performed. [Nanomedicine] Abstract

Progesterone Receptor Attenuates STAT1-Mediated IFN Signaling in Breast Cancer

Breast cancer cells lacking the progesterone receptor (PR) exhibited higher levels of IFN-stimulated gene (ISG) RNA, the transcriptional end point of IFN activation, indicating that unliganded PR alone could decrease transcription of ISGs. Moreover, the absence of PR led to increased recruitment of STAT1, STAT2, and IRF9 to ISG promoters. [J Immunol] Abstract

Metformin Prevention of Doxorubicin Resistance in MCF-7 and MDA-MB-231 Involves Oxidative Stress Generation and Modulation of Cell Adaptation Genes

Researchers investigated oxidative stress and inflammatory-related pathways during the induction of doxorubicin resistance in MCF-7 and MDA-MB-231 human breast cancer cells (DOX-res group), and evaluated metformin-induced cellular responses that resulted in the prevention of doxorubicin resistance. Microarray analysis demonstrated that DOX-res changed the expression of genes involved in oxidative stress and the TGF- β1 pathway. [Sci Rep] Full Article

Mapping Bromodomains in Breast Cancer and Association with Clinical Outcome

Scientists explored the expression of the bromodomain (BRD) family at a transcriptomic level in breast cancer, and its association with patient survival. In HER2 positive tumors the combined analyses of BRD2, BAZ1A, TRIM33 and ZMYND8 showed a detrimental relapse free survival. Similarly, the combined analysis of BRD2, BAZ1A, PHIP, TRIM33, KMT2A, ASH1L, PBRM1, correlated with an extremely poor overall survival. [Sci Rep] Full Article

H₂O₂ Induces Nuclear Transport of the Receptor Tyrosine Kinase c-MET in Breast Cancer Cells via a Membrane-Bounded Retrograde Trafficking Mechanism

Investigators showed that knocking down either coatomer protein complex subunit gamma 1 or Sec61 translocon beta subunit attenuated the accumulation of full-length nuclear hepatocyte growth factor receptor (c-MET). However, a c-MET kinase inhibitor did not block nuclear c-MET transport. [J Biol Chem] Abstract | Full Article

Upregulation of FOXP4 in Breast Cancer Promotes Migration and Invasion through Facilitating EMT

The authors found that FOXP4 promoted cell proliferation, migration, as well as invasion of breast cancer cells. Furthermore, FOXP4 also facilitated epithelial-mesenchymal transition. ChIP, qChIP assay, and dual luciferase reporter assay were used to examine whether Snail was a downstream target of FOXP4. [Cancer Manag Res] Full Article

The Role of ZNF143 in Breast Cancer Cell Survival through the NAD(P)H Quinone Dehydrogenase 1-p53-Beclin1 Axis under Metabolic Stress

Scientists found that breast cancer cells with low expression levels of a zinc-finger protein, ZNF143, showed better survival than control cells under starvation, which was compromised with chloroquine, an autophagy inhibitor. ZNF143 knockdown affected the stability of p53, which showed a dependence on MG132, a proteasome inhibitor. [Cells] Full Article

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Updates on the CDK4/6 Inhibitory Strategy and Combinations in Breast Cancer

The authors summarize the molecular background and clinical efficacy of cyclin-dependent kinase (CDK) 4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of breast cancer. [Cells] Abstract

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Lynparza Approved in EU for the Treatment of Germline BRCA-Mutated HER2-Negative Advanced Breast Cancer

AstraZeneca and MSD Inc. announced that the European Commission has approved Lynparza as a monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, and who have human epidermal growth factor receptor 2 (HER2)-negative locally-advanced or metastatic breast cancer. [AstraZeneca] Press Release

US FDA Approves IBRANCE^® (Palbociclib) for the Treatment of Men with HR⁺, HER2^– Metastatic Breast Cancer

Pfizer announced that the FDA approved a supplemental New Drug Application to expand the indications for palbociclib in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR⁺), human epidermal growth factor receptor 2-negative (HER2^–) advanced or metastatic breast cancer. [Pfizer, Inc.] Press Release

Racism Rife at Top South African University, Says Report

A damning report that says racism is entrenched at the University of Cape Town has reignited discussions about how to erase the divisive legacy of colonialism at South Africa’s top research institutions. [Nature News] Editorial

FDA, New York Attorney General Go after Stem Cell Clinics

On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist] Editorial

NEW Keystone Symposia: Tumor Metabolism
March 8-12, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Position – Breast Cancer Research (Massachusetts General/Harvard Medical School)

NEW Postdoctoral Training Fellow – Gene Function & Breast Cancer (The Institute of Cancer Research)

Faculty Position – Breast and Ovarian Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellowship – Breast Cancer Research (Washington University School of Medicine)

Postdoctoral Position – Breast Cell Atlas (University of Cambridge)

Professor – Breast Cancer (University Hospitals Cleveland Medical Center)

Postdoctoral Researcher – BRCA1/2-Deficient Tumors (University of Oxford)

Postdoctoral Associate – Cancer Immunology (The Jackson Laboratory)

Scientific Review Officer – Breast Cancer (METAvivor)

Postdoctoral Fellow – Cancer Bioinformatics (BC Cancer Research Center, PHSA)

Postdoctoral Fellow – Breast Cancer Research (City of Hope)

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