Mammary Cell News Volume 9.09 | Mar 9 2017

TOP STORY

The Shc1 Adaptor Simultaneously Balances Stat1 and Stat3 Activity to Promote Breast Cancer Immune Suppression

It was previously identified that the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, was essential for promoting breast cancer immune suppression. Scientists showed that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Loss of ERα Induces Amoeboid-Like Migration of Breast Cancer Cells by Downregulating Vinculin

The authors determined that loss of the estrogen receptor alpha (ERα) in the invasive front and in lymph node metastasis in human breast cancer is significantly correlated with lymphatic metastasis. Using in vivo and in vitro experiments, they demonstrated that ERα inhibits breast cancer metastasis. [Nat Commun] Full Article

AKR1B1 Promotes Basal-Like Breast Cancer Progression by a Positive Feedback Loop that Activates the EMT Program

Investigators showed that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with basal-like breast cancer (BLBC) and predicts poor prognosis in breast cancer patients. NF-κB up-regulated Twist2 expression, fulfilling a positive feedback loop that activated the epithelial–mesenchymal transition program and enhanced cancer stem cell–like properties in BLBC. [J Exp Med] Full Article

ZNF503/Zpo2 Drives Aggressive Breast Cancer Progression by Down-Regulation of GATA3 Expression

Loss of GATA3 is associated with aggressive breast cancer development. Scientists identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. [Proc Natl Acad Sci USA] Abstract

Integrin-β4 Identifies Cancer Stem Cell-Enriched Populations of Partially Mesenchymal Carcinoma Cells

Carcinoma cells with mesenchymal features are often more resistant to therapy and may serve as a source of relapse. Researchers sought to determine whether such cells could be further stratified into functionally distinct subtypes. They found that a basal epithelial marker, integrin-β4, can be used to enable stratification of mesenchymal-like triple-negative breast cancer cells that differ from one another in their relative tumorigenic abilities. [Proc Natl Acad Sci USA] Full Article

Kinome-Wide RNA Interference Screen Reveals a Role for PDK1 in Acquired Resistance to CDK4/6 Inhibition in ER-Positive Breast Cancer

To discover mechanisms of resistance to CDK4/6 inhibitors, the authors used a kinome-wide siRNA screen to identify kinases that, when downregulated, promote sensitivity to ribociclib. They identified 3-phosphoinositide dependent protein kinase 1 (PDK1) as the top siRNA that sensitized ER⁺ MCF-7 cells to ribociclib. [Cancer Res] Abstract

NR1D1 Recruitment to Sites of DNA Damage Inhibits Repair and Is Associated with Chemosensitivity of Breast Cancer

Scientists identified a novel function of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited both non-homologous end joining and homologous recombination double strand breaks repair, and delayed the clearance of γH2AX DNA repair foci that formed after treatment of doxorubicin. [Cancer Res] Abstract

Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

While the multiple endocrine neoplasia type 1 gene functions as a tumor suppressor in a variety of cancer types, researchers explored its oncogenic role in breast tumorigenesis. Their analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. [Cell Rep] Full Article | Graphical Abstract

WEE1 Inhibition Targets Cell Cycle Checkpoints for Triple Negative Breast Cancers to Overcome Cisplatin Resistance

Cisplatin is one of the most commonly used therapeutic drugs for cancer therapy, yet prolonged cisplatin treatment frequently results in drug resistance. The authors demonstrated that cisplatin activates ATR, CHK1 and WEE1, which shut down DNA replication and attenuate cisplatin induced-lethality. [Sci Rep] Full Article

Volatile Metabolomic Signature of Human Breast Cancer Cell Lines

Volatile organic compounds, from the headspace of cultured breast cancer cells and normal human mammary epithelial cells, were collected by headspace solid-phase microextraction and analyzed by gas chromatography combined with mass spectrometry, thus defining a volatile metabolomic signature. [Sci Rep] Full Article

CLINICAL RESEARCH

Circulating Gamma-Glutamyl Transferase and Development of Specific Breast Cancer Subtypes: Findings from the Apolipoprotein Mortality Risk (AMORIS) Cohort

Researchers investigated the association between gamma-glutamyl transferase (GGT) and development of specific breast cancer subtypes based on estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Positive associations were found between serum GGT and development of ER⁺, ER⁻ and PR⁺ breast cancers compared to controls and of ER⁺/PR⁺ tumors. [Breast Cancer Res] Full Article

Role of Runx2 in Breast Cancer-Mediated Bone Metastasis

The authors provide an outline of breast cancer mediated bone metastasis and summarize the recent development on the regulation of Runx2 expression by microRNAs which can lead to novel molecular therapeutics for the same. [Int J Biol Macromol] Abstract

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

H3 Biomedicine to Present New Data from Recent Research Advancements

H3 Biomedicine Inc. announced that company scientists will present one oral and five poster presentations. Presentations will include first disclosures and updates on H3’s lead programs in clinical development; H3B-6454, H3B-8800 and H3B-6527. [Press release from H3 Biomedicine Inc. (Business Wire, Inc.) discussing research to be presented at the 2017 American Association of Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release

BerGenBio Enters Collaboration with MSD Focused on Clinical Evaluation of BGB324 in Combination with KEYTRUDA^® (Pembrolizumab) in Advanced Lung and Breast Cancer

BerGenBio ASA announced it has entered into a collaborative agreement with Merck & Co., Inc. focused on the clinical evaluation of BGB324 with KEYTRUDA^® in patients with advanced non-small cell lung cancer and triple-negative breast cancer. [BerGenBio ASA] Press Release

The Union for International Cancer Control and Pfizer Announce next Phase of Global Grants Initiative Supporting Metastatic Breast Cancer Patients

Pfizer has committed funding to continue the next phase of their pioneering grants initiative to address the unique challenges facing metastatic breast cancer patients around the globe. [Pfizer Inc.] Press Release

$2.8 Million in Federal Grants to Jax Scientists to Target Triple-Negative Breast Cancers

Two grants from the U.S. Department of Defense totaling $2.8 million will support Jackson Laboratory research in one of the most deadly forms of breast cancer, known as triple-negative breast cancer. [Jackson Laboratory] Press Release

GSBS Dean Awarded $1.1 Million DOD Grant

Biomedical scientist Rajkumar Lakshmanaswamy, Ph.D., has received a $1.1 million research grant from the U.S. Department of Defense (DOD) to study how early pregnancy reduces a woman’s risk for breast cancer. [Texas Tech University Health Sciences Center El Paso] Press Release

Open-Data Contest Unearths Scientific Gems — and Controversy

When a prestigious medical journal challenged scientists to analyze data from a pivotal blood-pressure study in search of new findings, hundreds of researchers around the world rushed to sign up. The contest, sponsored by the New England Journal of Medicine, offered scientists a rare opportunity to access detailed trial data that otherwise might have remained proprietary for another year — if not indefinitely. But the competition, whose winners were announced on 7^th March, also illustrates the tension between speeding access to data and protecting the interests of those who laboured to collect them. [Nature News] Editorial

Prominent British Geneticist Offers Defense in Long-Running Misconduct Investigation

A leading UK academic has spoken publicly for the first time about a byzantine saga involving allegations of research misconduct in papers that stemmed from his research group at University College London. Geneticist David Latchman told Nature that although he did not scrutinize some of the papers sufficiently to detect errors, he also did not produce or directly supervise any of the images at the heart of the allegations. [Nature News] Editorial

NEW American Society of Gene & Cell Therapy (ASGCT)
May 10-13, 2017
Washington, D.C., United States

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

NEW Postdoctoral Position – Breast Cancer (Memorial Sloan Kettering Cancer Center)

NEW Postdoctoral Research Scholar – Breast Tumor Growth (University of Iowa)

NEW Postdoctoral Fellow – Proteoglycans (Thomas Jefferson University)

NEW Postdoctoral Fellow – Cancer Research (Houston Methodist Research Institute)

Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine)

Senior Faculty Position – Epidemiology (Institute of Cancer Research)

Cancer Bioinformatician – Breast Cancer (Institute of Cancer Research)

Assistant or Associate Professor – Breast Cancer (Roswell Park Cancer Institute)

Postdoctoral Associate – Mammary Stem Cell and Cancer Biology (University of Miami)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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