Mammary Cell News Volume 10.37 | Sep 20 2018

TOP STORY

Ubiquitin Ligase RNF8 Suppresses Notch Signaling to Regulate Mammary Development and Tumorigenesis

RNF8 acted as a negative regulator of Notch signaling by ubiquitylating the active NOTCH1 protein, leading to its degradation. Deficiency of RNF8 sensitized breast cancer cells to combination of pharmacological inhibitors of Notch signaling and poly(ADP-ribose) polymerase, suggesting implications for treatment of breast cancer associated with impaired RNF8 expression or function. [J Clin Invest] Full Article | Graphical Abstract

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A Small Molecule Targeting Myoferlin Exerts Promising Anti-Tumor Effects on Breast Cancer

Scientists found WJ460 as one of the lead compounds exerting anti-metastatic activity in the nanomolar range in breast cancer cells. Proteomic and biochemical studies identified myoferlin as the direct target of WJ460. [Nat Commun] Full Article

Differentiation-State Plasticity Is a Targetable Resistance Mechanism in Basal-Like Breast Cancer

Increased activity of many chromatin modifier enzymes, including BRD4, were observed in drug tolerant persister (DTP) cells. Co-treatment with the PI3K/mTOR inhibitor BEZ235 and the BET inhibitor JQ1 prevented changes to the open chromatin architecture, inhibited the acquisition of a DTP state, and resulted in robust cell death in vitro and xenograft regression in vivo. [Nat Commun] Full Article

Therapeutically Active RIG-I Agonist Induces Immunogenic Tumor Cell Killing in Breast Cancers

Treatment with retinoic acid-inducible gene-I (RIG-I) agonist resulted in upregulation and mitochondrial localization of RIG-I and activation of pro-inflammatory transcription factors STAT1 and NF-κB. RIG-I agonist triggered the extrinsic apoptosis pathway and pyroptosis, a highly immunogenic form of cell death in breast cancer cells. [Cancer Res] Abstract | Full Article

Glycoprotein Nmb Is Exposed on the Surface of Dormant Breast Cancer Cells and Induces Stem Cell-Like Properties

3D sphere cultures induced higher expression of cancer stem cell genes and epithelial-mesenchymal transition -inducing transcription factor (EMT-TF) genes than did the 2D monolayer cultures. 3D culture also induced cell surface expression of glycoprotein nmb on limited numbers of cells in the spheres, whereas the 2D cultures did not. [Cancer Res] Abstract

Regulation of Cellular Heterogeneity and Rates of Symmetric and Asymmetric Divisions in Triple-Negative Breast Cancer

Tumor cells expressing the cytokeratin K14 possess a differentiation state that is associated with that of normal luminal progenitors, and K14-negative cells are in a state closer to that of mature luminal cells. Researchers showed that cells could transition between these states through asymmetric divisions, which produced one K14⁺ and one K14⁻ daughter cell, and that these asymmetric divisions contributed to the generation of cellular heterogeneity. [Cell Rep] Full Article | Graphical Abstract

AR-PDEF Pathway Promotes Tumor Proliferation and Upregulates MYC-Mediated Gene Transcription by Promoting MAD1 Degradation in ER-Negative Breast Cancer

Scientists found that prostate-derived Ets factor (PDEF) was overexpressed in estrogen receptor (ER)-negative breast cancer (BC) tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with androgen receptor (AR) expression in ER-negative BC, and PDEF transcription was positively regulated by AR. [Mol Cancer] Full Article

Psoralen Induced Cell Cycle Arrest by Modulating Wnt/β-Catenin Pathway in Breast Cancer Cells

Investigators demonstrated that psoralen significantly inhibited cell proliferation by inducing G0/G1 phase arrest in MCF-7 cells and G2/M phase arrest in MDA-MB-231 cells. The expression of Fra-1 was reduced and Axin2 was promoted both in MCF-7 and MDA-MB-231 cells after psoralen treatment. [Sci Rep] Full Article

Contradictory mRNA and Protein Misexpression of EEF1A1 in Ductal Breast Carcinoma Due to Cell Cycle Regulation and Cellular Stress

Researchers found that EEF1A1 mRNA levels in breast carcinomas were low due to EEF1A1 allelic copy number loss, found in 27% of tumors, and cell cycle-specific expression, because mRNA levels are high in G1 and low in proliferating cells. In contrast, high eEF1α1 protein levels protected tumor cells from stress-induced cell death. [Sci Rep] Full Article

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How Does Estrogen Work on Autophagy?

The authors summarize the estrogenic effectors reported to affect autophagy, subcellular distribution and translocation of estrogen receptors, autophagy-targeted transcription factors, miRNAs, and histone modifications regulated by E2. [Autophagy] Abstract

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

Halozyme Announces Approval of Subcutaneous Formulation of Trastuzumab (Herceptin^®) in Canada

Halozyme Therapeutics, Inc. announced that Roche has received approval from Health Canada for a subcutaneous formulation of trastuzumab for the treatment of patients with HER2-positive breast cancer. This is a co-formulation with Halozyme’s proprietary recombinant human hyaluronidase enzyme. [Halozyme, Inc.] Press Release

OV – Updated LiPlaCis Data Positions LiPlaCis and Its DRP for an FDA Breakthrough Therapy Designation Application for Breast Cancer

Oncology Venture A/S (OV) announce the fourth update from the ongoing LiPlaCis^® Phase II study. In the ongoing study, the data points to the possibility of obtaining a Breakthrough Therapy designation by the FDA. [Oncology Venture A/S] Press Release

Mersana Announces FDA Lifts Partial Clinical Hold for XMT-1522

Mersana Therapeutics, Inc. announced that the U.S. FDA has lifted the partial clinical hold on the Phase I study of XMT-1522. Mersana and the FDA reached alignment on changes to the protocol, including increased monitoring as well as the exclusion of patients with advanced hepatic impairment. [Mersana Therapeutics] Press Release

CrownBio Licenses Translational Breast Cancer Models of Resistance and Metastasis

Crown Bioscience has reached an agreement with the University of Utah to license and commercialize the university’s unique collection of patient-derived xenograft models for breast cancer. [Crown Bioscience Inc.] Press Release

This Research Groups Seeks to Expose Weaknesses in Science—and They’ll Step on Some Toes If They Have To

Metaresearchers investigate how scientists operate, and how they can slip off the rails. Their main focus is questionable research practices, such as massaging data and selective reporting of statistical tests. [ScienceInsider] Editorial

African and Asian Researchers Are Hampered by Visa Problems

Going to a conference? Good luck getting a visa. Researchers from Africa and Asia still encounter much greater obstacles in getting visas to visit other countries for work than do those from Europe or North America. They are also less likely to visit another country for research, according to a global survey of academics’ movements. [Nature News] Editorial

NSF Spells Out New Sexual Harassment Policy: Talk to Us

Starting next month, universities must tell the National Science Foundation (NSF) in Alexandria, Virginia, if any faculty members with NSF grants have been found guilty of sexual and other forms of harassment, or if they have suspended them for any reason. But NSF won’t pull its funding if institutions can assure the agency that another faculty member can take over the research project. [ScienceInsider] Editorial

NEW European Society for Medical Oncology (ESMO) 2019 Congress
September 27-October 1, 2019
Barcelona, Spain

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

NEW Research Assistant II – Breast Medical Oncology (MD Anderson Cancer Center)

NEW 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)

Research Assistant II – Breast Medical Oncology (MD Anderson Cancer Center)

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

Tenure-Track Assistant Professor – Breast Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Fellow/Research Scientist – Cancer Research (Icahn School of Medicine at Mount Sinai)

Postdoctoral Positions – Breast Cancer Research (UPMC Hillman Cancer Center)

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