Mammary Cell News Volume 11.28 | Jul 25 2019

TOP STORY

A ZEB1/p53 Signaling Axis in Stromal Fibroblasts Promotes Mammary Epithelial Tumors

ZEB1 deletion in stromal fibroblasts increased acetylation, expression and recruitment of p53 to FGF2/7, VEGF and IL6 promoters, thereby reducing their production and secretion into the surrounding stroma. Importantly, p53 ablation in ZEB1 stroma-deleted mammary tumors sufficiently recovers the impaired cancer growth and progression. [Nat Commun] Full Article

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Integrated Analyses of Murine Breast Cancer Models Reveal Critical Parallels with Human Disease

Through integrative in vitro and in vivo studies, researchers identified copy number alterations in key extracellular matrix proteins including collagen 1 type 1 alpha 1 and chondroadherin that drove metastasis in mouse models. In addition to copy number alterations, they observed a propensity of the tumors to modulate tyrosine kinase-mediated signaling through mutation of phosphatases such as PTPRH in the MMTV-PyMT mouse model. [Nat Commun] Full Article

Scaffold Stiffness Influences Breast Cancer Cell Invasion via EGFR-Linked Mena Upregulation and Matrix Remodeling

MDA-MB-231 breast tumor spheroids were embedded in ‘low’ and ‘high’ stiffness 3D hydrogels comprised of methacrylated gelatin/collagen I, a material that allowed for physiologically-relevant changes in stiffness while matrix density was held constant. Cells in high stiffness materials exhibited delayed invasion, but more abundant actin-enriched protrusions, compared to those in low stiffness. [Matrix Biol] Abstract

GPER-Induced Signaling Is Essential for the Survival of Breast Cancer Stem Cells

Scientists showed greater expression of G protein-coupled estrogen receptor-1 (GPER) in breast cancer stem cells (BCSCs) than non-BCSCs of three patient-derived xenografts of ER^–/PR⁺ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. [Int J Cancer] Abstract

FABP7 Is a Key Metabolic Regulator in HER2⁺ Breast Cancer Brain Metastasis

The authors conducted an in silico screening analysis and identified that increased levels of fatty acid-binding protein 7 correlated with a lower survival and higher incidence of brain metastases in breast cancer patients. They validated these findings using HER2⁺ breast cancer brain metastases cells compared with parental breast cancer cells. [Oncogene] Abstract

SOX7 Regulates MAPK/ERK-BIM Mediated Apoptosis in Cancer Cells

Mechanistically, SOX7 induced cellular apoptosis through upregulation of genes associated with both P38 and apoptotic signaling pathway, as well as prevented the proteasome mediated degradation of pro-apoptotic protein BIM. Treatment of either a proteasome inhibitor MG132 or bortezomib, or with a p-ERK/MEK inhibitor U0126 attenuated the SOX7 promoted BIM degradation. [Oncogene] Abstract

Glucocorticoid Receptor Modulation Decreases ER-Positive Breast Cancer Cell Proliferation and Suppresses Wild-Type and Mutant ER Chromatin Association

In vitro cell proliferation assays were used to assess estrogen receptor (ER)-mediated breast cancer cell proliferation following glucocorticoid receptor (GR) modulation. ER chromatin association following ER/GR co-liganding was measured using global ChIP sequencing and directed ChIP analysis of proliferative gene enhancers. [Breast Cancer Res] Full Article

Berberine Attenuates XRCC1-Mediated Base Excision Repair and Sensitizes Breast Cancer Cells to the Chemotherapeutic Drugs

Researchers found that berberine (BBR) arrested cells in the cell cycle S phase and induced DNA breaks. Cell growth analysis showed BBR sensitized MDA-MB-231 cells to cisplatin, camptothecin and methyl methanesulfonate; however, BBR had no synergistic effects with hydroxurea and olaparib. [J Cell Mol Med] Full Article

E2F1 Drives Breast Cancer Metastasis by Regulating the Target Gene FGF13 and Altering Cell Migration

Transcriptomic profiling of E2F1 knockout tumors identified a role for E2F1 as a master regulator of a suite of pro-metastatic genes, but also uncovered E2F1 target genes with an unknown role in pulmonary metastasis. High expression of one of these genes, Fgf13, was associated with early human breast cancer metastasis in a clinical dataset. [Sci Rep] Full Article

Plasticity of Patient-Matched Normal Mammary Epithelial Cells Is Dependent on Autologous Adipose-Derived Stem Cells

The adipose-derived stem cell (ADSC) secretome was analyzed from five normal breast reduction patients and contained elevated levels of growth factors, cytokines and proteins mediating invasion. ADSC/ADSC secretomes were tested for their influence on the function of primary mammary epithelial cells, and tumor epithelial cells using cell culture assays. [Sci Rep] Full Article

Paracrine Crosstalk between Fibroblasts and ER⁺ Breast Cancer Cells Dreates an IL1β-Enriched Niche That Promotes Tumor Growth

The authors used modified patient-derived organoid cultures and demonstrated that constitutively secreted cytokines from normal breast fibroblasts initiated a paracrine signaling mechanism with estrogen receptor positive breast cancer cells which resulted in the creation of an IL1β-enriched microenvironment. They found that this paracrine signaling mechanism was shared between normal and activated fibroblasts. [iScience] Abstract | Graphical Abstract

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Notch Signaling in Breast Cancer: From Pathway Analysis to Therapy

The authors critically evaluate existing Notch inhibitory drugs and strategies and summarize the previous discoveries, current understanding, and recent developments in support of Notch receptors as therapeutic targets in breast cancer. [Cancer Lett] Abstract

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

OSE Immunotherapeutics Receives a Grant from the French National Research Agency to Validate New Targets Linked to Myeloid Cells and Identify Innovative New Immunotherapies in Oncology

OSE Immunotherapeutics announced that its DC-TARGET project has been selected by the French National Research Agency to be awarded a grant up to €800,000 following the “AAPG 2019” call for proposals assessment process. In particular, this immuno-oncology research program will explore tissues from triple negative breast cancer, a cancer with a high risk of progression. [OSE Immunotherapeutics (GlobeNewswire, Inc.)] Press Release

Damon Runyon Cancer Research Foundation Grants Fellowship Awards to 15 Young Scientists

The recipients of this prestigious, four-year award are outstanding post-doctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators across the country. Damon Runyon encourages the nation’s most promising young scientists to pursue careers in cancer research by providing them with independent funding ($231,000 total) to work on creative high-risk projects. [Damon Runyon Cancer Research Foundation] Press Release

Scientists Doing Basic Studies of Human Brain Win Longer Reprieve from Clinical Trials Reporting Rule

US scientists who challenged a new rule that would require them to register their basic studies of the human brain and behavior in a federal database of clinical trials have won another reprieve. The National Institutes of Health in Bethesda, Maryland, says it now understands why some of that kind of research won’t easily fit the format of ClinicalTrials.gov, and the agency has delayed the reporting requirements for another two years. [Science Magazine] Editorial

What Boris Johnson’s Leadership Could Mean for Science

Boris Johnson has been selected as the United Kingdom’s new prime minister — and is poised to lead the country out of the European Union. At the forefront of many scientists’ minds are questions about how Johnson’s leadership, including his support for a ‘no deal’ Brexit, will affect research. They fear that British science has much to lose from a messy departure from the EU. [Nature News] Editorial

NEW EMBL Conference: Cancer Genomics
November 4-6, 2019
Heidelberg, Germany

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

NEW Scientific Communications Coordinator (STEMCELL Technologies Inc.)

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

Research Officer – Tumor Progression in Breast and Prostate Cancer (Garvan Institute of Medical Research)

Scientific Officer – Breast Cancer Organoid/3D Cell Culture Facility (Institute of Cancer Research London)

Scientific Officer – Patient Derived Xenografts (Institute of Cancer Research)

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)

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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