Mammary Cell News Volume 11.33 | Aug 29 2019

TOP STORY

Metastatic-Niche Labeling Reveals Parenchymal Cells with Stem Features

Scientists present a system in which metastatic cancer cells released a cell-penetrating fluorescent protein, which was taken up by neighboring cells and enabled spatial identification of the local metastatic cellular environment. Using this system, tissue cells with low representation in the metastatic niche could be identified and characterized within the bulk tissue. [Nature] Abstract

(Ranked by impact factor of the journal)

Therapeutic Genome Editing of Triple-Negative Breast Tumors Using a Noncationic and Deformable Nanolipogel

Researchers report the synthesis and application of a noncationic, deformable, and tumor-targeted nanolipogel system for CRISPR genome editing in triple negative breast cancer (TNBC) tumors. They demonstrated that tumor-targeted nanolipogel systems mediated a potent CRISPR knockout of Lipocalin 2, a known breast cancer oncogene, in human TNBC cells in vitro and in vivo. [Proc Natl Acad Sci USA] Abstract

Modeling of Cisplatin-Induced Signaling Dynamics in Triple-Negative Breast Cancer Cells Reveals Mediators of Sensitivity

Systems-level analysis-using quantitative time-resolved signaling data and phenotypic responses, in combination with mathematical modeling-identified that the activation status of cell-cycle checkpoints determinesdcisplatin sensitivity in triple negative breast cancer (TNBC) cell lines. Specifically, inactivation of the cell-cycle checkpoint regulator MK2 or G3BP2 sensitized cisplatin-resistant TNBC cell lines to cisplatin. [Cell Rep] Full Article | Graphical Abstract

LOXL2-Mediated H3K4 Oxidation Reduces Chromatin Accessibility in Triple-Negative Breast Cancer Cells

Lysyl oxidase-like 2 (LOXL2) and H3K4ox were higher in triple-negative breast cancer cell lines and patient-derived xenografts than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox was located primarily in heterochromatin, where it was involved in chromatin compaction. [Oncogene] Full Article

Inhibition of the Transcriptional Kinase CDK7 Overcomes Therapeutic Resistance in HER2-Positive Breast Cancers

Investigators describe a novel treatment strategy that targeted cyclin-dependent kinase 7 (CDK7) in human epidermal growth factor receptor 2 (HER2) inhibitor-resistant breast cancer. They showed that both HER2 inhibitor-sensitive (HER2iS) and HER2iR breast cancer cell lines exhibited high sensitivity to THZ1, a newly identified covalent inhibitor of the transcription regulatory kinase CDK7. [Oncogene] Full Article

Depletion of the Transcriptional Coactivator Amplified in Breast Cancer 1 (AIB1) Uncovers Functionally Distinct Subpopulations in Triple-Negative Breast Cancer

The authors report that established triple negative breast cancer (TNBC) cell lines, as well as cells from a TNBC patient-derived xenograft that survived chemotherapy treatment in vitro, expressed lower levels of AIB1 protein. The surviving cell population had an impaired tube-formation phenotype when cultured onto basement membrane, a property shared with TNBC cells that survivde shRNA-mediated depletion of AIB1. [Neoplasia] Full Article

A Biomimetic 3D Model of Hypoxia-Driven Cancer Progression

Scientists present a biomimetic cancer model based on a collagen matrix synthesized through a biologically inspired process. They compared in this environment the responses of two breast tumor lineages characterized by different molecular patterns and opposite clinical behaviors: MCF-7 that belonged to the luminal A subtype connected to an indolent course, and basal-like MDA-MB-231 connected to high-grade and aggressive disease. [Sci Rep] Full Article

Pheno-Seq – Linking Visual Features and Gene Expression in 3D Cell Culture Systems

Investigators introduced “pheno-seq” to directly link visual features of 3D cell culture systems with profiling their transcriptome. As prototypic applications breast and colorectal cancer spheroids were analyzed by pheno-seq. They identified characteristic gene expression signatures of epithelial-to-mesenchymal transition that were associated with invasive growth behavior of clonal breast cancer spheroids. [Sci Rep] Full Article

Higher Glucose Enhances Breast Cancer Cell Aggressiveness

Using lowly metastatic MCF-7 and highly metastatic MDA-MB231 breast cancer cells, the authors established how glucose metabolism regulated actin and the biochemical changes that led to alterations of cell mechanical properties. They found that higher glucose increased glycolytic enzymes, glucose uptake, migration speed, kinesin, Ki-67, and NFkB expressions, and hybrid EMT phenotype activation. [Nutr Cancer] Abstract

Suppression of the Proliferation and Invasion of Breast Cancer Cells by ST7L Occurs through Inhibition of Activation of Wnt/GSK-3β/β-Catenin Signaling

Researchers found that suppression of tumorigenicity 7-like (ST7L) expression was frequently downregulated in breast cancer cell lines. Functional assays revealed that ST7L overexpression significantly inhibited the proliferation and invasion of breast cancer cells, while ST7L silencing showed opposite effect. [Clin Exp Pharmacol Physiol] Abstract

Cyclin E Overexpression in Human Mammary Epithelial Cells Promotes Epithelial Cancer-Specific Copy Number Alterations

Investigators showed that non-transformed human mammary epithelial cell clones that survived aberrant mitoses had a specific and reproducible pattern of chromosomal copy number (CNA) alterations that they characterized and termed the cyclin E CNA signature. Using a number of computational approaches, they showed that this signature resembled one specific CNA pattern enriched in differentiated epithelial-like tumors of the breast and ovary. [iScience] Abstract | Graphical Abstract

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Role of the Microenvironment in Regulating Normal and Cancer Stem Cell Activity: Implications for Breast Cancer Progression and Therapy Response

Understanding the crosstalk between mammary stem cells and their microenvironment will provide new insights into how an altered breast tissue microenvironment could contribute to breast cancer development, progression and therapy response and the implications of this for the development of novel therapeutic strategies to target cancer stem cells. [Cancers] Full Article

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

The authors collect available evidence on the biological relevance and clinical utility of programmed cell death ligand 1 expression in breast cancer, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. [Oncologist] Abstract | Full Article

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Arvinas Announces the Initiation of Patient Dosing in a First-in-Human Phase I Study of ARV-471, an Estrogen Receptor-Targeting PROTAC^® Protein Degrader

Arvinas, Inc. announced the initiation of patient dosing in its second clinical program. The Phase I clinical trial of ARV-471, an oral estrogen receptor (ER)-targeting PROTAC^® protein degrader, will evaluate the safety, tolerability, and pharmacokinetics of ARV-471 in patients with locally advanced or metastatic ER positive/HER2 negative breast cancer. [Arvinas, Inc.] Press Release

European Commission Approves Roche’s Tecentriq in Combination with Abraxane for People with PD-L1-Positive, Metastatic Triple-Negative Breast Cancer

Roche announced that the European Commission has approved 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. [Roche] Press Release

Baylor Awarded CPRIT Grants to Support Cancer Research

Baylor College of Medicine has been awarded more than $17.4 million by the Cancer Prevention & Research Institute of Texas (CPRIT) to support new cancer research and programs, core facilities and recruitment of new faculty. More than 70 grants were awarded to institutions across Texas, totaling close to $136 million to advance the fight against cancer, including nine grants to Baylor College of Medicine. [Baylor College of Medicine] Press Release

Younger Scientists Need Better Support

Letters from research funders to university leaders rarely raise eyebrows. But a letter sent this month by the heads of the United Kingdom’s three largest medical-research funders did just that. [Nature News] Editorial

FDA Warns Testing Companies: Don’t Tell Patients How Their DNA Influences Response to Specific Drugs

Amid a boom in genetic testing that aims to predict a person’s response to medication, the FDA has been quietly pressuring a handful of companies to stop reporting results to patients about how their genes may interact with specific drugs. [STAT News] Editorial

NEW NF-kB, JAK-STAT & MAPK in Health, Disease & Therapy
October 7-11, 2019
Suzhou, China

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NEW Postdoctoral Fellow – Breast and Prostate Cancer (Mayo Clinic Comprehensive Cancer Center)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Assistant – Endocrinology in Breast Cancer and Diabetes (Northwell Health)

Bioinformatician – Breast Cancer (Royal College of Surgeons)

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

Postdoctoral Fellow – Breast Cancer (Monash University)

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

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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