Mammary Cell News Volume 11.25 | Jul 4 2019

TOP STORY

Subclonal Cooperation Drives Metastasis by Modulating Local and Systemic Immune Microenvironments

Researchers showed that minor subclones of breast cancer cells expressing IL11 and FIGF cooperated to promote metastatic progression and generate polyclonal metastases composed of driver and neutral subclones. Expression profiling of the epithelial and stromal compartments of monoclonal and polyclonal primary and metastatic lesions revealed that this cooperation was indirect, mediated through the local and systemic microenvironments. [Nat Cell Biol] Abstract

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Death Effector Domain-Containing Protein Induces Vulnerability to Cell Cycle Inhibition in Triple-Negative Breast Cancer

Investigators revealed that Death Effector Domain-containing DNA-binding protein (DEDD), which was overexpressed in >60% of triple negative breast cancers, drove a mitogen-independent G1/S cell cycle transition through cytoplasm localization. The gain of cytosolic DEDD enhanced cyclin D1 expression by interacting with heat shock 71-kDa protein 8. [Nat Commun] Full Article

SETD1A Protects from Senescence through Regulation of the Mitotic Gene Expression Program

Cell cycle arrest in SETD1A knockdown senescent cells was independent of mutations in p53, RB and p16, known senescence mediators; instead, it was sustained through transcriptional suppression of SKP2, which degraded p27 and p21. Rare cells escaping senescence by restoring SKP2 expression displayed genomic instability. [Nat Commun] Full Article

TBX2 Interacts with Heterochromatin Protein 1 to Recruit a Novel Repression Complex to EGR1-Targeted Promoters to Drive the Proliferation of Breast Cancer Cells

The authors showed that siRNA knockdown of TBX2, Early Growth Response 1 (EGR1), Heterochromatin Protein 1 (HP1) isoforms and the generic HP1-associated corepressor protein KAP1 all resulted in growth inhibition of TBX2-expressing breast cancer cells. They showed that TBX2 interacted with HP1 through a conserved HP1-binding motif in its N-terminus, which in turn led to the recruitment of KAP1 and other associated proteins. [Oncogene] Abstract

Duplex-Specific Nuclease-Mediated Amplification Strategy for Mass Spectrometry Quantification of MiRNA-200c in Breast Cancer Stem Cells

Researchers combined a duplex-specific nuclease-mediated amplification strategy with liquid chromatography-tandem mass spectrometry for use in this study. They designed the substrate peptide GDKAVLGVDPFR, which contained the reporter peptide AVLGVDPFR and a tryptic cleavage site in combination with a biotinylated DNA sequence that was complementary to a target miRNA. [Anal Chem] Full Article

Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition

Scientists studied the overlap between metastatic stem cells and tumor-initiating cells in the MMTV-PyMT model. Their results showed that in the MMTV-PyMT model, Lin⁻CD90⁻ALDH^high cells retained a high tumor-initiating potential in orthotopic transplants, in contrast to Lin⁻CD24⁺CD90⁺, which retained higher metastatic capacity. [Stem Cell Reports] Full Article | Graphical Abstract

Overexpression of Matrix Metalloproteinase-9 in Breast Cancer Cell Lines Remarkably Increases the Cell Malignancy Largely via Activation of Transforming Growth Factor Beta/SMAD Signalling

A recombinant plasmid expressing mouse matrix metalloproteinase 9 was generated and transiently transfected into three different breast cancer cell lines. Cell Counting Kit-8 and colony formation assay were used to study cell viability. [Cell Prolif] Full Article

HNRNPA2/B1 Is Upregulated in Endocrine-Resistant LCC9 Breast Cancer Cells and Alters the miRNA Transcriptome When Overexpressed in MCF-7 Cells

Investigators examine the expression of writers, readers, and erasers of N(6)-methyladenosine and report that Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRNPA2/B1) expression was higher in tamoxifen-resistant LCC9 breast cancer cells as compared to parental, tamoxifen-sensitive MCF-7 cells. To examine how increased expression of HNRNPA2/B1 affected miRNA expression, HNRNPA2/B1 was transiently overexpressed in MCF-7 cells for whole genome miRNA profiling. [Sci Rep] Full Article

BRCA1 Regulates the Cancer Stem Cell Fate of Breast Cancer Cells in the Context of Hypoxia and Histone Deacetylase Inhibitors

Scientists examined the role of the tumor suppressor BRCA1 and hypoxia in the regulation of cancer cell stemness using genetically matched breast cancer cell lines. They found that BRCA1, a multifunctional protein involved in DNA repair and epigenetic regulation, played a critical role in the regulation of cancer stem cell-like characteristics. [Sci Rep] Full Article

DC-SCRIPT Deficiency Delays Mouse Mammary Gland Development and Branching Morphogenesis

Analysis revealed that DC-SCRIPT was expressed in mouse mammary epithelium and that DC-SCRIPT deficiency delayed mammary gland morphogenesis in vivo. Analysis of 3D mammary gland organoid cultures confirmed that loss of DC-SCRIPT dramatically delayed mammary organoid branching in vitro. [Dev Biol] Abstract

Taxifolin Inhibits Breast Cancer Cells Proliferation, Migration and Invasion by Promoting Mesenchymal to Epithelial Transition via β-Catenin Signaling

The antineoplastic activity of taxifolin was evaluated in MDA-MB-231 and 4-T1 cells by crystal violet assay and colony formation assay. The effects of taxifolin on migration and invasion were determined by wound healing assay and Transwell assay, respectively. [Life Sci] Abstract

Breast Cancer Invasion and Progression by MMP-9 through Ets-1 Transcription Factor

The role of Ets-1 in MCF-7 and MDA-MB-231 breast cancer cells was studied by RNA-interference in combination with pull down and ChIP assays to identify the regulation of MMP-9 in these cell lines. Results showed that transfection of Ets-1 siRNA in breast cancer cell lines resulted in downregulation of Ets-1 and MMP-9. [Gene] Abstract

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The d16HER2 Splice Variant: A Friend or Foe of HER2-Positive Cancers?

The authors summarize the existing evidence regarding the pathobiological functions of the d16HER2 variant in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and discuss its current and future value with regard to risk assessment and treatment choices in HER2-positive disease. [Cancers] Full Article

Emerging Role of Genomics and Cell-Free DNA in Breast Cancer

As a result of decreasing costs, both solid and liquid-based genomics have an increasingly important role in clinical trials’ screening procedures and are gradually being incorporated into clinical practice. Notwithstanding the great potential, its clinical utility is still a matter of debate and clinicians need to be aware of caveats in interpreting resulting data. [Curr Treat Options Oncol] Abstract

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CHMP Recommends EU Approval of Roche’s Tecentriq in Combination with Abraxane as an Initial Treatment for People with PD-L1-Positive, Metastatic Triple-Negative Breast Cancer

Roche announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq^® plus chemotherapy for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors have PD-L1 expression and who have not received prior chemotherapy for metastatic disease. [F. Hoffmann-La Roche Ltd] Press Release

MU Receives $8.6 Million Federal Grant for New Biomedical Research Center

The University of Missouri (MU) announced that researchers in the College of Agriculture, Food and Natural Resources have received an $8.6 million grant from the National Institutes of Health to establish a new national research center. The Swine Somatic Cell Genome Editing Center will focus on aiding the development of biomedical treatments for human diseases such as cystic fibrosis. [The University of Missouri] Press Release

University Releases Reports from Investigation of Prominent Geneticist

On July 1^st, University College London released reports from misconduct investigations into the lab of David Latchman, who was a prominent geneticist at the university and is now head of Birkbeck, University of London. The documents describe evidence of research fraud in Latchman’s research group from separate investigations conducted in 2014, 2015, and 2016. [The Scientist] Editorial

Why India Is Striking Back against Predatory Journals

According to 2015 estimates, more than 8,000 predatory journals churn out more than 400,000 items a year, and India — which has also seen a spurt in high-quality scientific publications – contributes more than one-third of the articles in predatory publications. Last month, India launched its latest salvo against the ‘pay and publish trash’ culture that sustains predatory journals. [Nature News] Editorial

Exclusive: FDA Enforcement Actions Plummet Under Trump

From monitoring clinical trials and approving medicines and vaccines, to ensuring the safety of blood transfusions, medical devices, groceries, and more, the FDA is one of the nation’s most vital watchdogs. By several measures, however, FDA’s compliance and enforcement actions have plummeted since President Donald Trump took office, Science has found. [ScienceInsider] Editorial

Germany’s Prestigious Max Planck Society Conducts Huge Bullying Survey

Most of the scientists who work for one of the world’s richest and most prestigious basic research organizations, the Max Planck Society (MPS) in Germany, have pride and trust in their institutes — but cases of sexual discrimination and bullying occur regularly, and nearly half of foreign scientists working for the MPS don’t feel they fit in. [Nature News] Editorial

NEW Victorian Comprehensive Cancer Centre (VCCC) Research Conference 2019
September 16-17, 2019
Victoria, Australia

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

NEW 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)

Senior Global Medical Director – Breast Cancer (F.Hoffmann-La Roche)

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

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

Postdoctoral Fellows – Bioinformatics (IRCCS European Institute of Oncology)

Postdoctoral Associate – Cancer Immunology (The Jackson Laboratory)

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