Mammary Cell News Volume 10.33 | Aug 23 2018

TOP STORY

Imbalance of the Reciprocally Inhibitory Loop between the Ubiquitin-Specific Protease USP43 and EGFR/PI3K/AKT Drives Breast Carcinogenesis

Scientists reported that the ubiquitin-specific protease USP43 was physically associated with the chromatin remodeling NuRD complex and catalyzed H2BK120 deubiquitination. USP43 also existed in the cytoplasm, where it was phosphorylated by AKT, enabling its binding to the 14-3-3β/ε heterodimer and sequestration in the cytoplasm. [Cell Res] Abstract

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Protease-Activated Receptor2 Promotes Actomyosin Dependent Transforming Microvesicles Generation from Human Breast Cancer

Treatment of cells with protease-activated receptor 2 activators facilitated microvesicle generation by activating three independent signaling cascades. MAPK, signaled through activating MLCK followed by MLC phosphorylation to alter myosin organization whereas, P38 reorganized actin dynamics by the sequential activation of MK2 and HSP27. [Mol Carcinog] Abstract

Inhibitory Effects of Low Intensity Pulsed Ultrasound on Osteoclastogenesis Induced In Vitro by Breast Cancer Cells

Low intensity pulsed ultrasound treatment impaired MDA-MB-231 cell dependentosteoclast differentiation and produced a reduction of osteoclast markers such as cathepsin k, matrix metalloproteinase 9 and tartrate resistant acid phosphatase, suggesting its role as an effective and safe adjuvant in bone metastasis management. [J Exp Clin Cancer Res] Full Article

The Transcriptome of Human Mammary Epithelial Cells Infected with the HCMV-DB Strain Displays Oncogenic Traits

The transcriptome of human cytomegalovirus (HCMV)-DB-infected human mammary epithelial cells presented the characteristics of a pro-oncogenic cellular environment with upregulated expression of numerous oncogenes, enhanced activation of pro-survival genes, and upregulated markers of cell proliferation, stemcellness and epithelial mesenchymal transition that was confirmed by enhanced cellular proliferation and tumorsphere formation in vitro. [Sci Rep] Full Article

Indibulin Dampens Microtubule Dynamics and Produces Synergistic Antiproliferative Effect with Vinblastine in MCF-7 Cells: Implications in Cancer Chemotherapy

Indibulin reduced inter-kinetochoric tension, produced aberrant spindles, activated mitotic checkpoint proteins Mad2 and BubR1, and induced mitotic arrest in MCF-7 cells. Indibulin-treated MCF-7 cells underwent apoptosis-mediated cell death. [Sci Rep] Full Article

Thioridazine Inhibits Self-Renewal in Breast Cancer Cells via DRD2-Dependent STAT3 Inhibition, but Induces a G1 Arrest Independent of DRD2

Researchers showed that thioridazine induced a G1 arrest and a loss in cell viability in all tested cell lines. However, the reduction in proliferation and cell viability was independent of dopamine receptor 2 (DRD2) and STAT3. [J Biol Chem] Abstract | Full Article

Inhibition of Smoothened in Breast Cancer Cells Reduces CAXII Expression and Cell Migration

Investigators demonstrated that smoothened (SMO) silencing resulted in a reduction of CAXII expression at the mRNA and protein level. This led to a decrease in cell migration, which was restored when cells were treated with an SMO agonist, sag dihydrochloride (SAG), but not when cells were co-treated with SAG and the carbonic anhydrase inhibitor acetazolamide. [J Cell Physiol] Abstract

Antitumor Activity of Cell-Penetrant Kinin B1 Receptor Antagonists in Human Triple-Negative Breast Cancer Cells

The authors found that the compounds SSR240612, NG67, and N2000 were more toxic to MDA-MB-231 cells in comparison with low- or non-B1R expressing MCF-10A normal human mammary epithelial cells and COS-1 cells, respectively. [J Cell Physiol] Abstract

Malignant Canine Mammary Epithelial Cells Shed Exosomes Containing Differentially Expressed MicroRNA That Regulate Oncogenic Networks

Canine mammary epithelial cell (CMEC) and canine mammary tumor (CMT) cell lines shed round, “cup-shaped” exosomes approximately 150–200 nm, and were immunopositive for exosomal marker CD9. Three hundred thirty-eight unique miRs were detected, with 145 having greater than ±1.5-fold difference between one or more CMT and CMEC samples. [BMC Cancer] Full Article

RUNX3 Epigenetic Inactivation Is Associated with Estrogen Receptor Positive Breast Cancer

Researchers showed that the expression of runt-related transcription factor 3 (RUNX3) was high in MCF10A but not in MCF7 and SKBR3 cell lines, while the RUNX3 promoter showed hypermethylation in MCF7 but not in MCF10A and SKBR3. [J Histochem Cytochem] Abstract

Single Cell Tracking of Breast Cancer Cells Enables Highly Accurate Prediction of Sphere Formation Using Only Early Doubling Information

Scientists individually tracked 1,127 single MCF-7 and 696 single T47D human breast tumor cells over the course of 14 days. They correlated early cell division with eventual sphere formation. At 24 hours post seeding, they could predict total spheres on day 14 with 98% accuracy in both lines. [iScience] Abstract | Full Article | Graphical Abstract

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Cancer Cell Plasticity: Impact on Tumor Progression and Therapy Response

The authors provide an overview of the dynamic transition for cancer cell states, the mechanisms governing cell plasticity and their impact on tumor progression, metastasis and therapy response. Understanding the mechanisms involved in cancer cell plasticity will provide insights for establishing new therapeutic interventions. [Semin Cancer Biol] Abstract

Effects of Isoflavones on Breast Tissue and the Thyroid Hormone System in Humans: A Comprehensive Safety Evaluation

Investigators evaluate and summarize the evidence from interventional and observational studies addressing potential unintended effects of isoflavones on the female breast in healthy women as well as in breast cancer patients and on the thyroid hormone system. [Arch Toxicol] Full Article

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CCAB Partners with Immunobiochem as It Launches New Co-development Strategy to Advance Early-Stage Biotech Companies

The Centre for the Commercialization of Antibodies and Biologics (CCAB) and ImmunoBiochem Corporation have announced an agreement that will see CCAB provide a new investment to help advance ImmunoBiochem’s novel breast cancer therapeutic candidate one step closer to the clinic. [CCAB] Press Release

SOLAR-1 Trial of Novartis Investigational Alpha-Specific PI3K Inhibitor BYL719 (Alpelisib) Meets Primary Endpoint in HR⁺/HER2^– Advanced Breast Cancer with PIK3CA Mutation

Novartis announced the global Phase III SOLAR-1 trial evaluating the investigational alpha-specific PI3K inhibitor BYL719 has met the primary endpoint showing an improvement in progression-free survival. [Novartis AG] Press Release

Initiation of Biosceptre’s Phase I Clinical Trial for First-in-Class Oncology Vaccine BIL06v

Biosceptre has initiated its Phase I clinical trial of the peptide vaccine BIL06v, with the first patient treated at the initial trial site. The trial will accept broad cancer indications with primary focus on prostate and lung cancer patients who are refractory to, or have refused, standard of care treatment. Breast, colorectal and other cancer patients will also be accepted. [Biosceptre] Press Release

Scientists Retrain to Join Fight against Disease

The University’s Medical Research Council Institute of Genetics and Molecular Medicine has partnered with the School of Informatics on a £2 million training program for early career scientists. The scheme is recruiting talented scientists with no formal training in the life sciences to help solve the most pressing questions in biomedicine and become future research leaders. [The University of Edinburgh] Press Release

Trump Science-Adviser Pick Faces US Senate Committee

Meteorologist Kelvin Droegemeier is in the hot seat, speaking before a US Senate committee during a hearing on his nomination to head the White House Office of Science and Technology Policy. An early focus of the questions from lawmakers centered on scientific competition from China and how, if he’s confirmed, Droegemeier would address sexual harassment in research. [Nature News] Editorial

Japanese Authorities Recommend Not Regulating Gene Editing

A Japanese government panel announced that it recommends regulating only genetically modified organisms that have had foreign genes permanently introduced into their genomes and not those whose endogenous genes have been edited, according to NHK World-Japan. [The Scientist] Editorial

In Defiance of Trump’s Budget, Senate Poised to Boost NIH Funding—Again

Ignoring President Donald Trump’s proposed budget, the Senate is setting up to approve a $2 billion boost in funding for the National Institutes of Health (NIH). [Fierce Biotech] Editorial

Hundreds of Chimps at the NIH Await Retirement. This Senator Wants to Help

Sen. Bill Cassidy is trying to help hundreds of chimpanzees enjoy an easy retirement in his home state of Louisiana. The Republican is pushing for an amendment to a major appropriations bill winding its way through Congress that would force the National Institutes of Health (NIH) to make good on a 2015 promise to move all its chimps out of research facilities. [STAT News] Editorial

NEW ESMO Breast Cancer 2019
May 2-4, 2019
Berlin, Germany

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NEW 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)

Cancer Faculty Investigators – Cancer Research (University of Alabama at Birmingham)

Postdoctoral Research Fellow – Immuno/Oncology of Breast Cancer (Henry M. Jackson Foundation)

Research Assistant/Associate – Breast Cancer Therapeutics (King’s College London)

Research Assistant/Associate – Translational Breast Cancer Research (Icahn School of Medicine at Mount Sinai)

Postdoctoral Research Scientist – DNA Repair Assay, Breast Cancer (Columbia Center for Radiological Research)

Postdoctoral Position – Breast Cancer (University of Trento)

Postdoctoral Research Fellow – Translational Mitochondrial Research (Fred Hutch Cancer Research Center)

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