Mammary Cell News Volume 11.39 | Oct 10 2019

TOP STORY

The Glucocorticoid Receptor Interferes with Progesterone Receptor-Dependent Genomic Regulation in Breast Cancer Cells

Using a progesterone⁺/glucocorticoid (GR)⁺ breast cancer cell line, the authors report that either glucocorticoid-free or dexamethasone-activated GR inhibited progestin-dependent gene expression associated to epithelial-mesenchymal-transition and cell proliferation. [Nucleic Acids Res] Full Article

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Modeling Breast Cancer Using CRISPR/Cas9-Mediated Engineering of Human Breast Organoids

Researchers demonstrated that breast epithelial organoids could be generated from human reduction mammoplasties, thus creating a tool to study the clonal evolution of breast cancer. To recapitulate de novo oncogenesis, they exploited CRISPR/Cas9 for targeted knock-out of four breast cancer-associated tumor suppressor genes in mammary progenitor cells from six donors. [J Natl Cancer Inst] Abstract

SOD2 Acetylation on Lysine 68 Promotes Stem Cell Reprogramming in Breast Cancer

Acetylated SOD2 promoted hypoxic signaling via increased mitochondrial reactive oxygen species (mtROS). mtROS, in turn, stabilized hypoxia-induced factor 2α, a transcription factor upstream of “stemness” genes such as Oct4, Sox2, and Nanog. [Proc Natl Acad Sci USA] Abstract

Chemotherapy-Induced Senescent Cancer Cells Engulf Other Cells to Enhance Their Survival

Using time-lapse and confocal microscopy to observe interactions of cells in treated tumors, scientists showed that chemotherapy-induced senescent cells frequently engulf both neighboring senescent or nonsenescent tumor cells at a remarkable frequency. Engulfed cells were processed through the lysosome and broken down, and cells that engulfed others obtained a survival advantage. [J Cell Biol] Abstract

Single-Cell Chromatin Analysis of Mammary Gland Development Reveals Cell-State Transcriptional Regulators and Lineage Relationships

Investigators provided a single-cell resource of chromatin accessibility for murine mammary development from the peak of fetal mammary stem cell functional activity in late embryogenesis to the differentiation of adult basal and luminal cells. They found that the chromatin landscape within individual cells predicts both gene accessibility and transcription factor activity. [Cell Rep] Full Article | Graphical Abstract

HUNK Phosphorylates EGFR to Regulate Breast Cancer Metastasis

The authors showed that hormonally up-regulated neu-associated kinase (HUNK) phosphorylated epidermal growth factor receptor (EGFR) at T654, enhancing receptor stability and downstream signaling. They found that increased phosphorylation of T654 EGFR correlated with increased epithelial to mesenchymal, migration and invasion, and metastasis. [Oncogene] Full Article

Long Noncoding RNA LINC02582 Acts Downstream of miR-200c to Promote Radioresistance through CHK1 in Breast Cancer Cells

Lin Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacted with deubiquitinating enzyme ubiquitin specific peptidase 7 to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. [Cell Death Dis] Full Article

Hypoxia Modulates Stem Cell Properties and Induces EMT through N-Glycosylation of EpCAM in Breast Cancer Cells

Scientists evaluated the role of N-glycosylation of epithelial cell adhesion molecule (EpCAM) in stemness and epithelial–mesenchymal transition (EMT) characteristics. EpCAM overexpression increased the expression of stemness markers and EMT markers under the condition of hypoxia in breast cancer. [J Cell Physiol] Abstract

d-a-Tocopheryl Polyethylene Glycol 1000 Succinate and a Small-Molecule Survivin Suppressant Synergistically Induce Apoptosis in SKBR3 Breast Cancer Cells

The D-alpha-tocopheryl polyethylene glycol succinate-YM155 combination acted synergistically to reduce specifically the viability of SKBR3 cells. The combination of these agents reduced activation of the AKT pathway, decreased survivin and Bcl-2 levels, and induced caspase-dependent and independent apoptosis via the mitochondrial pathway. [Sci Rep] Full Article

Induced Tamoxifen Resistance Is Mediated by Increased Methylation of E-cadherin in Estrogen Receptor-Expressing Breast Cancer Cells

Treatment with demethylating agent 5-azacytidine increased the expression of E-cadherin thus verifying a role of methylation in its silencing and, moreover, 5-azacytidine treatment also re-sensitized MCF-7-TAM cells to tamoxifen, as evaluated by assays for viability, apoptosis and migration potential. [Sci Rep] Full Article

ECM-Mimetic Multiresponsive Nanobullets Targeted against Metastasizing Circulating Tumor Clusters in Breast Cancer

Bullet shaped ellipsoidal nanostructures of size 600 ± 11.3 nm and 281.9 ± 5.3 nm with 2.2 aspect ratio were self-assembled using inorganic and organic GRAS biomaterials to preferentially target tumor-causing circulating tumor clusters. Negatively-charged chondroitin sulfate in presence of gelatin guides unidirectional growth of calcium carbonate mesocrystals to form nanobullets, mediatef CD44 targeting of CTCs. [Ann Biomed Eng] Abstract

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Metabolic Crosstalk in the Breast Cancer Microenvironment

The authors address current knowledge on this metabolic crosstalk within the breast tumor microenvironment (TME). Improved understanding of how metabolism in the TME modulates cancer development and evasion of tumor-suppressive mechanisms may provide clues for novel anticancer therapeutics directed to metabolic targets. [Eur J Cancer] Abstract

The Regulatory Role of MicroRNAs in Breast Cancer

Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs, thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. [Int J Mol Sci] Full Article

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Insilico Signs $200M AI Drug Discovery Partnership with China’s CTFH

Shortly after publishing a paper demonstrating how its artificial intelligence programs could generate viable lead compounds in just a few weeks, Insilico Medicine has signed a dual-program discovery collaboration with Jiangsu Chia Tai Fenghai Pharmaceutical worth up to $200 million. Focused on previously undruggable targets in triple-negative breast cancer, the deal includes an upfront payment along with potential milestones and sales-based royalties pegged to any eventual products. [Questex LLC.] Editorial

Seattle Genetics Announces Initiation of Phase III Clinical Trial of Tucatinib in Combination with Ado-Trastuzumab Emtansine (T-DM1, Kadcyla^®) for Patients with Advanced or Metastatic HER2-Positive Breast Cancer

Seattle Genetics, Inc. announced dosing of the first patient in HER2CLIMB-02, a randomized Phase III clinical trial evaluating investigational agent tucatinib versus placebo, in combination with standard-of-care ado-trastuzumab emtansine, for patients with locally advanced or metastatic HER2-positive breast cancer. This trial is intended to support registration in the US Tucatinib is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2. [Seattle Genetics, Inc.] Press Release

BriaCell Doses First Patient in Phase I/IIa Study Evaluating Bria-IMT™ in Combination with INCMGA00012 and Epacadostat in Patients with Advanced Breast Cancer

BriaCell Therapeutics Corp. announced that it has initiated dosing in a Phase I/IIa clinical study of its lead product candidate, Bria-IMT™, in combination with Incyte’s INCMGA00012 and epacadostat in patients with advanced breast cancer whose disease has progressed following standard of care therapies. [BriaCell Therapeutics Corp.] Press Release

Quanterix Announces Recipients of Annual Accelerator Grant Program

Quanterix Corporation announced Shelli Kesler, Ph.D., and Ashley Henneghan, PhD., MSN, from the School of Nursing at the University of Texas at Austin, as the winners of its annual Accelerator Grant Program for their research proposal, “Neurodegenerative and Inflammatory Predictors of Cancer Related Cognitive Impairment in Breast Cancer Patients.” [Quanterix Corporation] Press Release

NEW Tumor Immunology and Immunotherapy
November 17-20, 2019
Boston, Massachusetts, United States

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NEW Research Assistant – Breast and Endocrine Tumors (University of Texas MD Anderson Cancer Center)

Chief Editor – Nature Ageing (Nature Research)

Postdoctoral Position – Cancer Biology (Memorial Sloan Kettering Cancer Center)

Research Scientist – Breast Cancer (The University of Pittsburgh)

Postdoctoral Researcher – Nanomedicine and Immunoengineering (University of California San Diego)

Postdoctoral Research Fellow – Epithelial Growth in Development and Cancer (Fred Hutchinson Cancer Research Center)

Project Scientist – Breast and Hematological Tumors (Cedars-Sinai)

Postdoctoral Research Scientist – Role of Cancer-Associated Fibroblast Metabolism in Breast Cancer (Cancer Research UK Beatson Institute)

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

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

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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