Mammary Cell News Volume 10.40 | Oct 11 2018

TOP STORY

ΔNp63-Driven Recruitment of Myeloid-Derived Suppressor Cells Promotes Metastasis in Triple-Negative Breast Cancer

Researchers found that high levels of the transcription factor ΔNp63 correlated with an increased number of myeloid-derived immunosuppressor cells in basal triple-negative breast cancer (TNBC) patients, and that ΔNp63 promoted tumor growth, progression, and metastasis in human and mouse TNBC cells. [J Clin Invest] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

LEM4 Confers Tamoxifen Resistance to Breast Cancer Cells by Activating Cyclin D-CDK4/6-Rb and ERα Pathway

Scientists showed that LEM4 overexpression accelerated tumor growth. Interaction with LEM4 stabilized CDK4 and Rb, promoted Rb phosphorylation and the G1/S phase transition. LEM4 depletion or combined tamoxifen and PD0332991 treatment significantly reversed tamoxifen resistance. [Nat Commun] Full Article

Activated Kinase Screening Identifies the IKBKE Oncogene as a Positive Regulator of Autophagy

Scientists demonstrated that the IKBKE oncoprotein was able to stimulate autophagy when overexpressed, an event frequently found in breast tumors, and that its activity was strictly required for breast cancer cells to support the autophagic process. Different oncogenic pathways typically involved in breast cancer, namely ERBB2 and PI3K-AKT-MTOR, also relied on IKBKE to control this process. [Autophagy] Full Article

C/EBPδ Links IL-6 and HIF-1 Signaling to Promote Breast Cancer Stem Cell-Associated Phenotypes

Investigators showed that deletion or depletion of C/EBPδ reduced the expression of stem cell factors and stemnness markers, sphere formation and self-renewal, along with growth of tumors and established experimental metastases in vivo. Their mechanistic data revealed C/EBPδ as a link that engaged two positive feedback loops, in part by directly targeting the IL-6 receptor gene, and, thus, amplifying IL-6 and HIF-1 signaling. [Oncogene] Abstract

Neratinib Is Effective in Breast Tumors Bearing Both Amplification and Mutation of ERBB2 (HER2)

Compared to HER2 amplification alone, in both patients and cultured cell lines, the co-occurrence of HER2 mutation and amplification was associated with poor response to trastuzumab and lapatinib, the standard-of-care anti-HER2 agents. In mice, xenografts established from a patient whose HER2-positive tumor acquired a D769Y mutation in HER2 after progression on trastuzumab-based therapy were resistant to trastuzumab or lapatinib but were sensitive to neratinib. [Sci Signal] Full Article

Therapeutic Activity of DCC-2036, a Novel Tyrosine Kinase Inhibitor, against Triple-Negative Breast Cancer Patient-Derived Xenografts by Targeting AXL/MET

The authors confirmed that DCC-2036 inhibited the proliferation, invasion, migration and epithelial-mesenchymal transition of triple-negative breast cancer (TNBC) cells as well as induced apoptosis. DCC-2036 significantly inhibited tumor growth and invasion of AXL/MET-high TNBC PDX tumors but not AXL/MET-low TNBC PDX tumors. [Int J Cancer] Abstract

Targeting Peroxiredoxin 1 Impairs Growth of Breast Cancer Cells and Potently Sensitizes these Cells to Prooxidant Agents

Peroxiredoxin-1 (PRDX1) downregulation significantly impaired the growth rate of MCF-7 and ZR-75-1 breast cancer cells. Likewise, xenotransplanted PRDX1-deficient MCF-7 cells presented a retarded tumor growth. Genetic targeting of PRDX1 or adenanthin, but not PRDX2, potently sensitized all six cancer cell lines studied, but not the non-cancerous cells, to glucose oxidase and ascorbate. [Br J Cancer] Abstract

Comparison of Breast Cancer Metastasis Models Reveals a Possible Mechanism of Tumor Aggressiveness

Researchers compared the overall miRNA expression profiles (miRNome) of the orthotopic and intravenous breast cancer metastasis models and identified significant miRNome changes between the two models. [Cell Death Dis] Full Article

MSCs Inhibit Tumor Progression and Enhance Radiosensitivity of Breast Cancer Cells by Down-Regulating Stat3 Signaling Pathway

Researchers investigated the potential of mesenchymal stem cell conditioned medium (MSC-CM) in sensitizing breast cancer to radiotherapy. MSC-CM reduced the ALDH-positive cancer stem cell population, modulated several potential stem cell markers, and decreased tumor migration, as well as metastasis. [Cell Death Dis] Full Article

Chrysophanol Selectively Represses Breast Cancer Cell Growth by Inducing Reactive Oxygen Species Production and Endoplasmic Reticulum Stress via AKT and Mitogen-Activated Protein Kinase Signal Pathways

Chrysophanol selectively inhibited cell proliferation and induced apoptosis of breast cancer cells but not of normal mammary ductal epithelial cells, MCF-12A. Reactive oxygen species overproduction by chrysophanol resulted in endoplasmic reticulum stress, leading to an increase in PERK, eIF2α, GADD153, and IRE1α levels in BT-474 and MCF-7 cells. [Toxicol Appl Pharmacol] Abstract

LGR5 Acts as a Target of miR-340-5p in the Suppression of Cell Progression and Drug Resistance in Breast Cancer via Wnt/β-Catenin Pathway

Overexpressed miR-340-5p inhibited cell proliferation and drug resistance to docetaxel with enhanced cell apoptosis of breast cancer cells. They found that LGR5 was a potential target of miR-340-5p. Knockdown of LGR5 inhibited cell proliferation and drug resistance to docetaxel with enhanced cell apoptosis of breast cancer cells. [Gene] Abstract

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BRCA Mutations: Is Everything Said?

The authors provide an overview of the current state of BRCA1 and BRCA2 mutation description and classification. They discuss whether there is a trend towards a more frequently described mutation type and what the proportion of pathogenic mutations is. [Breast Cancer Res Treat] Abstract

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TapImmune’s HER2/Neu-Targeted Breast Cancer Vaccine to be Studied in a Large Phase II Immunotherapy Combination Study Funded by an $11 Million U.S. Department of Defense Grant

TapImmune Inc. congratulates Mayo Clinic for being awarded a grant of $11 million from the U.S. Department of Defense. This grant will cover the costs of a large Phase II study of TapImmune’s HER2/neu-targeted breast cancer vaccine, TPIV110, in combination with another immunotherapeutic, trastuzumab, for treating women with HER2/neu-positive breast cancer. [TapImmune Inc.] Press Release

Atossa Genetics Completes Enrollment in Phase II Study of Topical Endoxifen in Women with Mammographic Breast Density

Atossa Genetics Inc. has completed enrollment in its Phase II study of Atossa’s proprietary Topical Endoxifen in women with mammographic breast density. [Atossa Genetics, Inc.] Press Release

Sermonix Launches Phase II Trial to Evaluate Investigational Oral Lasofoxifene as a Targeted Precision Treatment for Women with ESR1 Mutations in Metastatic Breast Cancer

Sermonix Pharmaceuticals LLC announced the launch of a Phase II trial for the treatment of metastatic breast cancer. [Sermonix Pharmaceuticals] Press Release

BriaCell Initiates Dosing in Phase I/IIa Combination Study with KEYTRUDA^® or YERVOY^®

BriaCell Therapeutics Corp. announced that it has initiated patient dosing in a Phase I/IIa study of its lead clinical candidate, Bria-IMT^™, in combination with pembrolizumab (KEYTRUDA^®) or ipilimumab (YERVOY^®). [BriaCell Therapeutics Corp.] Press Release

Argentina’s Scientists Struggle amid Slipping Peso and Rising Inflation

Juan Pablo Paz’s plans for a new cold-atom laboratory have slowly eroded over the past two years. Paz, a physicist at the University of Buenos Aires, won a US$1.1-million grant in February 2017 to set up the facility. But the money, awarded by the Inter-American Development Bank, was transferred to Paz through an Argentinian government agency that paid him in pesos. [Nature News] Editorial

Columbia University Postdocs Vote to Unionize

Postdocs at Columbia University voted to unionize, with representation from the United Auto Workers, according to The Associated Press. The organization represents the first postdoc union at a private university in the United States. [The Scientist] Editorial

Major Publishers File Second Lawsuit against ResearchGate

ResearchGate, a popular networking platform where scientists can post their published work, has a complicated relationship with academic publishers. A number of them have accused the site of illicitly disseminating copyrighted work, and two of these—Elsevier and the American Chemical Society—filed a lawsuit in Germany last year to try to force ResearchGate to change its practices. [The Scientist] Editorial

Surging R&D Spending in China Narrows Gap with United States

China’s total spending on R&D rose a robust 12.3% last year to a record 1.76 trillion yuan ($254 billion), according to a government report. Already second in the world in R&D spending behind the United States, China has narrowed the gap. [ScienceInsider] Editorial

Ghost Authorship Haunts Industry-Funded Clinical Trials

An analysis of industry-funded clinical trials has found that drug companies are often heavily involved in research — but are not always transparent about it. [Nature News] Editorial

NEW The 5^th Canadian Cancer Research Conference
November 3-5, 2019
Ottawa, Ontario, Canada

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

NEW Epigenetic Reprogramming of Enhancers During Breast Cancer Progression (Università degli Studi di Trento)

NEW Postdoctoral Fellowship – Epigenetics and RNA Biology (Umeå University)

Postdoctoral Research Fellow – Mammary Stem Cell Biology (University of Southampton)

Team Leader – ER Positive Breast Cancer (Institute of Cancer Research)

Assistant/Associate/Progessor – Department of Cancer Biology (University of Cincinnati)

Scientific Coordinator (Helmholtz Zentrum Munchen)

Postdoctoral Fellow – Immunotherapy of Breast Cancer (Boston University School of Medicine)

Postdoctoral Fellow – Stem Cells and Cancer (Albert Einstein College of Medicine)

Postdoctoral Position – Cancer Biology (GIGA – Universite de Liege)

Cancer Faculty Investigators – Breast Cancer (The University of Alabama)

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