Mammary Cell News Volume 11.14 | Apr 18 2019

TOP STORY

Diet High in Leucine May Fuel Breast Cancer’s Drug Resistance

A team of researchers has discovered an unexpected relationship between levels of the amino acid leucine and the development of tamoxifen resistance in ER+ breast cancer. Led by Senthil K. Muthuswamy, PhD, the researchers further identified a key protein that imports leucine into cells and modulates sensitivity to tamoxifen in ER+ cells in the lab setting. [Press release from Beth Israel Deaconess Medical Center discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer

Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. [Cell] Full Article | Press Release | Graphical Abstract

Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Mediated by a Reversible Drug-Tolerant State

Barcode-mediated clonal tracking and genomic sequencing of patient-derived xenograft tumors revealed that residual tumors remaining after treatment with standard frontline chemotherapies, doxorubicin combined with cyclophosphamide, maintained the subclonal architecture of untreated tumors, yet their transcriptomes, proteomes, and histologic features were distinct from those of untreated tumors. [Sci Transl Med] Abstract | Press Release

PDGFRα⁺ Stromal Adipocyte Progenitors Transition into Epithelial Cells during Lobulo-Alveologenesis in the Murine Mammary Gland

Scientists identified, in mice, the transition of a PDGFRα⁺ mesenchymal cell population into mammary epithelial progenitors. In addition to being adipocyte progenitors, PDGFRα⁺ cells make a de novo contribution to luminal and basal epithelia during mammary morphogenesis. [Nat Commun] Full Article

Specific Inhibition of Splicing Factor Activity by Decoy RNA Oligonucleotides

Investigators showed that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, could specifically bind to their respective splicing factors and inhibit their splicing and biological activities both in vitro and in vivo. [Nat Commun] Full Article | Press Release

BRCA1-Associated R-Loop Affects Transcription and Differentiation in Breast Luminal Epithelial Cells

BRCA1 knockdown in ERα+ luminal breast cancer cells increased intensity of the R-loop and reduced transcription of its neighboring genes. The deleterious effect of BRCA1 depletion on transcription was mitigated by ectopic expression of R-loop-removing RNase H1. [Nucleic Acids Res] Full Article

Loss of Sirtuin 1 Alters the Secretome of Breast Cancer Cells by Impairing Lysosomal Integrity

The authors discovered that reducing Sirtuin 1 levels decreased the expression of one particular subunit of the vacuolar-type H+ ATPase, which was responsible for proper lysosomal acidification and protein degradation. [Dev Cell] Full Article | Graphical Abstract

MYB Regulates the DNA Damage Response and Components of the Homology-Directed Repair Pathway in Human Estrogen Receptor-Positive Breast Cancer Cells

Investigators found that silencing MYB in the estrogen receptor-positive breast cancer cell line MCF-7 led to increased DNA damage accumulation, as marked by increased γ-H2AX foci following induction of double-stranded breaks. [Oncogene] Abstract

Vitamin C Supplementation Expands the Therapeutic Window of BETi for Triple Negative Breast Cancer

High-throughput screening revealed that vitamin C improved the efficacy of a number of structurally-unrelated bromodomain and extra-terminal inhibitors (BETi) including JQ1, I-BET762, I-BET151, and CPI-203 in treating triple negative breast cancer cells. [EBioMedicine] Full Article | Press Release

Baicalein Inhibits Fibronectin-Induced Epithelial-Mesenchymal Transition by Decreasing Activation and Upregulation of Calpain-2

Researchers investigated the effects of the flavonoid baicalein on fibronectin-induced epithelial-mesenchymal transition in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model. [Cell Death Dis] Full Article

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Current Landscape of Immunotherapy in Breast Cancer: A Review

The authors describe the current status of immunotherapy in breast cancer, highlighting its potential in both early-stage and metastatic disease. [JAMA Oncol] Abstract

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

Preventing Triple Negative Breast Cancer from Spreading

Researchers have found that a combination drug therapy reduces the spread of triple negative breast cancer to other locations of the body by 50 percent. [Press release from the University of Missouri discussing research presented at the 2019 Annual Endocrine Society Meeting, New Orleans] Press Release

OncoSec Announces Collaborative Research Agreement in HER2+ Breast Cancer Evaluating the Use of TAVO™ in Combination with Plasmid DNA Vaccines with a World Leading Academic Medical Center

OncoSec Medical Incorporated announced that they have entered into a collaborative research agreement to evaluate the use of OncoSec’s proprietary TAVO^PLUS in combination or sequence with a HER2-plasmid vaccine administered with OncoSec’s novel intratumoral delivery system. [OncoSec Medical, Inc.] Press Release

Harpoon Therapeutics Doses First Patient with a Mesothelin-Targeting T Cell Engager (HPN536) in Phase I/IIa Clinical Trial for Ovarian and Other Solid Tumor Cancers

Harpoon Therapeutics, Inc. announced that the first patient has been dosed with HPN536 in a Phase I/IIa clinical trial initially focused on ovarian cancer. HPN536 targets mesothelin, which is expressed on malignant cells of ovarian and pancreatic carcinoma, mesothelioma, non-small cell lung cancer and breast cancer. [Harpoon Therapeutics, Inc.] Press Release

California Protons Cancer Therapy Center Invites Patients to Enroll in Breast Cancer Study and Clinical Trial

California Protons Cancer Therapy Center announced two major efforts representing significant steps forward in breast cancer treatment research involving its noninvasive, targeted proton therapy. [California Protons Cancer Therapy Center (Business Wire, Inc.)] Press Release

GlycoMimetics Announces Plans to Initiate Breast Cancer Trial to Evaluate GMI-1359

GlycoMimetics, Inc. announced plans to initiate a clinical trial of GMI-1359 in breast cancer patients whose tumors have spread to bone. [GlycoMimetics, Inc.] Press Release

How US-China Political Tensions Are Affecting Science

In the latest twist, several US universities are expected this month to announce the actions they have taken against foreign scientists caught breaking rules concerning National Institutes of Health funding, according to comments made by agency director Francis Collins to the Senate Appropriations Committee. [Nature News] Editorial

‘Friendly’ Reviewers Rate Grant Applications More Highly

Peer reviewers are four times more likely to give a grant application an “excellent” or “outstanding” score rather than a “poor” or “good” one when they are chosen by the grant’s applicants, an analysis of Swiss funding applications has found. [Nature News] Editorial

NEW London Breast Meeting 2019
September 4-7, 2019
London, United Kingdom

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

NEW Postdoctoral Research Position – Molecular Biology & Cancer Research (Augusta University)

NEW Postdoctoral Fellowship (Lund University)

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

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 Associate – Cancer Immunology (The Jackson Laboratory)

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

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