Mammary Cell News Volume 11.31 | Aug 15 2019

TOP STORY

Autophagy Inhibition Elicits Emergence from Metastatic Dormancy by Inducing and Stabilizing Pfkfb3 Expression

Researchers report that elevated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) expression correlated with the appearance of aggressive breast cancers and reduced relapse-free survival, as well as enhanced breast cancer stem cell self-renewal and metastatic outgrowth. They observed an inverse relationship between Pfkfb3 expression and autophagy, which reduced Pfkfb3 expression and elicited cellular dormancy. [Nat Commun] Full Article

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PAK4 Suppresses RELB to Prevent Senescence-Like Growth Arrest in Breast Cancer

Mechanistically, a PAK4-RELB-C/EBPβ axis controlled the senescence-like growth arrest and a PAK4 phosphorylation residue was critical for RELB-DNA interaction, transcriptional activity and expression of the senescence regulator C/EBPβ. [Nat Commun] Full Article

Motility-Limited Aggregation of Mammary Epithelial Cells into Fractal-Like Clusters

Scientists showed that dispersed mammary epithelial cells organized into arrested, fractal-like clusters at low density in reduced epidermal growth factor. These clusters exhibited a branched architecture with a fractal dimension of D_f=1.7, reminiscent of diffusion-limited aggregation of nonliving colloidal particles. [Proc Natl Acad Sci USA] Abstract

DAXX Suppresses Tumor-Initiating Cells in Estrogen Receptor-Positive Breast Cancer Following Endocrine Therapy

Knockdown and overexpression approaches were used to investigate the role of death-associated factor 6 (DAXX) on stem/pluripotent gene expression, tumor initiating cell (TIC) survival in vitro and TIC frequency in vivo, and the mechanism by which DAXX suppressed TICs in estrogen receptor⁺ breast cancer. 17β-estradiol-mediated ER activation stabilized the DAXX protein, which was required for repressing stem/pluripotent genes, and TICs in vitro and in vivo. [Cancer Res] Abstract

Whole-Exome and Whole-Transcriptome Sequencing of Canine Mammary Gland Tumors

Researchers produced reliable whole-exome and whole-transcriptome sequencing data of 197 canine mammary cancers and their matched controls, annotated with rich clinical and biological features. The dataset provided useful reference points for comparative analysis with human cancers and for developing novel diagnostic and therapeutic technologies for cancers in pet dogs. [Cancer Res] Full Article

A Spontaneous Aggressive ERα⁺ Mammary Tumor Model Is Driven by Kras Activation

Transcriptome analyses over the course of oncogenesis revealed marked alterations associated with Ras activity in established tumors compared with preneoplastic tissues; in cell-intrinsic processes associated with mitosis, cell adhesion, and invasion; as well as in the surrounding tumor environment. [Cell Rep] Full Article | Graphical Abstract

circKDM4C Suppresses Tumor Progression and Attenuates Doxorubicin Resistance by Regulating miR-548p/PBLD Axis in Breast Cancer

Investigators demonstrated that circKDM4C significantly repressed breast cancer proliferation, metastasis, and doxorubicin resistance in vitro and in vivo. Mechanistically, using a dual-luciferase activity assay and AGO2 RNA immunoprecipitation, circKDM4C was identified as a miR-548p sponge. [Oncogene] Abstract

LSD1 Suppresses Invasion, Migration and Metastasis of Luminal Breast Cancer Cells via Activation of GATA3 and Repression of TRIM37 Expression

Mechanistically, LSD1 interacted with GATA3, a key luminal-specific transcription factor (TF), and their common target genes were highly related to breast cancer. LSD1 positively regulated GATA3 expression. It also repressed expression of TRIM37, a breast epithelial oncogene encoding a histone H2A ubiquitin ligase, and ELF5, a key TF gene for luminal progenitors and alveolar luminal cells. [Oncogene] Abstract

Aurora-A/ERK1/2/mTOR Axis Promotes Tumor Progression in Triple-Negative Breast Cancer and Dual-Targeting Aurora-A/mTOR Shows Synthetic Lethality

Scientists found that Aurora kinase A (Aur-A) and p-mTOR were highly expressed and positively associated with each other in triple negative breast cancer cells and tissues. Inhibition or knockdown of Aur-A decreased p-mTOR and suppressed cell proliferation and migration, whereas overexpression of Aur-A increased p-mTOR levels and promoted cell proliferation and migration, which was significantly abrogated by simultaneous silencing of mTOR. [Cell Death Dis] Full Article

HER2, Chromosome 17 Polysomy and DNA Ploidy Status in Breast Cancer; a Translational Study

The authors investigated whether isolated polysomy was present and how this effected human epidermal growth factor receptor-2 (HER2) status in six breast cancer cell lines and 97 breast cancer cases, using HER2 FISH and immunohistochemistry, DNA ploidy assessment and multiplex ligation dependent probe amplification. They observed no isolated polysomy of chromosome 17 in any cell line. [Sci Rep] Full Article

Involvement of the P2X7 Receptor in the Migration and Metastasis of Tamoxifen-Resistant Breast Cancer: Effects on Small Extracellular Vesicles Production

Investigators found that protein and mRNA expression of the P2X purinoreceptor 7 (P2X7) was higher in tamoxifen resistant MCF-7 (TAMR-MCF-7) cells than in control MCF-7 cells. P2X7 inhibition potently inhibited the migration of TAMR-MCF-7 cells and the liver metastasis burden of TAMR-MCF-7 cells in the spleen-liver metastasis experiment [Sci Rep] Full Article

Electromagnetic Fields Alter the Motility of Metastatic Breast Cancer Cells

Using a novel microfluidic platform, scientists found that metastatic breast cancer cells sensed and responded to the net direction of weak, asymmetric, non-contact induced electric fields (iEFs). iEFs inhibited epidermal growth factor receptor activation, prevented formation of actin-rich filopodia, and hindered the motility of EGF-treated breast cancer cells. [Commun Biol] Full Article

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PARP Inhibitor Resistance: A Tug-of-War in BRCA-Mutated Cells

The authors discuss how studies on resistance mechanisms have yielded important insights into the regulation of DNA double-strand break repair and replication fork protection, and how these studies could pave the way for novel treatment options to target resistance mechanisms or acquired vulnerabilities. [Trends Cell Biol] Full Article

Epithelial-to-Mesenchymal Transition and Invadopodia Markers in Breast Cancer: Lumican a Key Regulator

A great hallmark of breast cancer is the absence or presence of estrogen receptors ERα and ERβ, with a dominant role in cell proliferation, differentiation and cancer progression. Both receptors are related with Epithelial-to-Mesenchymal Transition since there is a relation between ERs and extracellular matrix (ECM) macromolecules expression, and therefore, cell-cell and cell-ECM interactions. [Semin Cancer Biol] Abstract

SETDB-1: A Potential Epigenetic Regulator in Breast Cancer Metastasis

Investigators discuss the histone methyltransferase SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1) and its role in breast cancer metastasis. SETDB1 serves as an exemplar of the difficulties faced when developing therapies that not only specifically target cancer cells but also the more elusive and aggressive stem cells that contribute to metastasis via epithelial-to-mesenchymal transition and confer resistance to therapies. [Cancers] Abstract | Download Full Article

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FDA Grants IDE Approval to Use Oncology Venture’s LiPlaCis DRP for Patient Selection in a Pivotal Phase III Study

Oncology Venture A/S informed that the FDA has approved an Investigational Device Exemption application for use of the company’s drug response predictor LiPlaCis DRP^® in a planned pivotal Phase III study. In parallel, the FDA is evaluating Oncology Venture’s Investigational New Drug application for the drug substance LiPlaCis^®, which is primarily being developed as a potential new treatment of metastatic breast cancer in heavily pre-treated patients. [Oncology Venture A/S] Press Release

Mustang Bio Announces $9.28 Million Grant to Fund Phase I Trial of CAR T Therapy MB-103 in HER2-Positive Breast Cancer with Brain Metastases

Mustang Bio, Inc. announced that City of Hope has received a $9.28 million grant from the California Institute for Regenerative Medicine to fund an ongoing Phase I clinical trial of MB-103 for the treatment of HER2-positive breast cancer with brain metastases. [Mustang Bio, Inc.] Press Release

$6M to Fund McGill-Based National Breast Cancer Research Team

As part of the federal government’s Stand Up to Cancer program, professors Nahum Sonenberg and Michael N. Pollak will lead a multidisciplinary “dream team” in the fight against metastatic breast cancer. [The McGill Reporter] Press Release

Novartis Ousted Top Scientists over Manipulation of Data for Gene Therapy

Novartis dismissed the top two scientists at its gene therapy division shortly after CEO Vas Narasimhan learned of internal data falsification that has since snowballed into a damaging scandal. [STAT New] Editorial

UC Faculty Members Quit Cell Press Editorial Boards over Impasse with Publisher

Some of the University of California’s (UC’s) most prominent scientists have announced they will resign from editorial boards of Cell Press to protest the continuing impasse between its owner, publishing giant Elsevier, and UC over subscription costs and open access to articles. [ScienceInsider] Editorial

NEW Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges
January 19-23, 2020
Keystone, Colorado, United States

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NEW Bioinformatician – Breast Cancer (Royal College of Surgeons)

NEW Postdoctoral Fellow – Breast Cancer (Royal College of Surgeons)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Fellow – T-Cell Immunotherapy in Cancers (Memorial Sloan Kettering Cancer Center)

Postdoctoral Fellow – Breast Cancer (Monash University)

Postdoctoral Fellow – Breast Cancer Research (Institute of Cancer Research)

Research Officer – Tumor Progression in Breast and Prostate Cancer (Garvan Institute of Medical 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)

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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