Mammary Cell News Volume 11.32 | Aug 22 2019

TOP STORY

Interplay between c-Src and the APC/C Co-Activator Cdh1 Regulates Mammary Tumorigenesis

Researchers report that Cdh1 suppressed the kinase activity of c-Src in an the anaphase promoting complex (APC)-independent manner. Depleting Cdh1 accelerated breast cancer cell proliferation and cooperated with PTEN loss to promote breast tumor progression in mice. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

RNF144A Functions as a Tumor Suppressor in Breast Cancer through Ubiquitin Ligase Activity-Dependent Regulation of Stability and Oncogenic Functions of HSPA2

Quantitative proteomics and biochemical analysis revealed that RING finger protein 144A (RNF144A) interacted with and targeted heat-shock protein family A member 2 (HSPA2), a putative oncoprotein that is frequently upregulated in human cancer and promotes tumor growth and progression, for ubiquitination and degradation. [Cell Death Differ] Abstract

Chromatin Remodeling in Response to BRCA2-Crisis

Investigators established an in vitro model for BRCA2-crisis that demonstrated chromatin remodeling and activation of an NF-κB survival pathway in response to transient BRCA2 depletion. Mechanistically, they identified BRCA2 chromatin binding, histone acetylation, and associated transcriptional activity as critical determinants of the epigenetic response to BRCA2-crisis. [Cell Rep] Full Article | Graphical Abstract

Dynamic Interactions between the Extracellular Matrix and Estrogen Activity in Progression of ER⁺ Breast Cancer

The authors used an estrogen responsive syngeneic mouse model to interrogate how a COL1A1-enriched fibrotic ECM modulated integrated hormonal responses in cancer progression. They orthotopically transplanted the estrogen receptor (ER)⁺ TC11 cell line into wild-type or collagen-dense syngeneic FVB/N female mice. [Oncogene] Full Article

circFBXW7 Inhibits Malignant Progression by Sponging miR-197-3p and Encoding a 185aa Protein in Triple-Negative Breast Cancer

Researchers performed cell proliferation, colony formation, transwell, wound healing and mouse xenograft assays to confirm the functions of circFBXW7. Overexpression of circFBXW7 obviously inhibited cell proliferation, migration and tumor growth in both in vitro and in vivo assays. [Mol Ther Nucleic Acids] Abstract | Full Article

Revealing the Biological Attributes of N-Glycan Isomers in Breast Cancer Brain Metastasis Using Porous Graphitic Carbon (PGC) Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

The expressions of N-glycan isomers derived from five breast cancer cell lines and one brain cancer cell line were investigated and compared to a brain-seeking cell line, 231BR, to acquire a better understanding of the role glycan isomers play in breast cancer brain metastasis. The high temperature nanoPGC-LC-MS/MS achieved an efficient isomeric separation and permitted the identification and quantitation of 144 isomers from 50 N-glycan compositions. [J Proteome Res] Abstract

Transcriptomic Analysis of Breast Cancer Stem Cells and Development of a pALDH1A1:mNeptune Reporter System for Live Tracking

The authors performed transcriptomic analysis to identify segregating gene expression in cancer stem cells (CSCs) and non-CSCs, sorted by Aldefluor assay. They observed that among aldehyde dehydrogenase activity (ALDH) associated genes, only ALDH1A1 isoform was increased in CSCs. [Proteomics] Abstract

Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and Is Traceable in the Circulating Extracellular Vesicles

Expression pattern of SPANXB1 was determined using matched primary cancer, lymph node metastatic tissues and circulating small extracellular vesicles. cDNA microarray analysis of triple negative breast cancer cells stably integrated with a metastasis suppressor SH3GL2 identified SPANXB1 as a potential target gene. [Sci Rep] Full Article

Chronic Cadmium Exposure Decreases the Dependency of MCF7 Breast Cancer Cells on ERα

Scientists modulated the expression of estrogen receptor alpha (ERα) and found that while the loss of ERα significantly impaired cancer cell growth, migration, invasion and anchorage-independent growth in both MCF7 and MCF7-Cd cells, cadmium-exposed cells retained a significant advantage in cell growth, migration, and invasion, and partially circumvented the loss of ERα. [Sci Rep] Full Article

Targeted Transcript Quantification in Single Disseminated Cancer Cells after Whole Transcriptome Amplification

Investigators found that absolute quantification outperformed relative quantification. They then validated the performance of our method on single cells of established breast cancer cell lines displaying distinct levels of HER2 protein. The different protein levels were faithfully reflected by transcript expression across the tested cell lines thereby proving the accuracy of the approach. [PLoS One] Full Article

Compression-Induced Expression of Glycolysis Genes in CAFs Correlates with EMT and Angiogenesis Gene Expression in Breast Cancer

Investigators showed that compressive stress induced glycolysis in human breast cancer associated fibroblast (CAF) cells and thereby contributed to the expression of epithelial to mesenchymal (EMT)- and angiogenesis-related genes in breast cancer cells. Lactate production was increased in compressed CAF cells, in a manner dependent on the expression of metabolic genes ENO2, HK2, and PFKFB3. [Commun Biol] Full Article

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Inflammatory Breast Cancer: a Separate Entity

Inflammatory breast cancer is characterized by florid tumor emboli that obstruct dermal lymphatics, leading to swelling and inflammation of the affected breast. Recent studies have focused on tumor cell intrinsic features, such as signaling through pathways involved in growth and stem-like behavior, as well as extrinsic features, such as the immune system, that can be leveraged to develop new potential therapies. [Curr Oncol Rep] Abstract

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FDA Approves Roche’s Rozlytrek (Entrectinib) for People with ROS1-Positive, Metastatic Non-Small Cell Lung Cancer and NTRK Gene Fusion-Positive Solid Tumors

Roche announced that the FDA has approved Rozlytrek™ for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer. The FDA has also granted accelerated approval to Rozlytrek for the treatment of adult and paediatric patients 12 years of age and older with solid tumours that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy [Roche] Press Release

City of Hope Scientist Receives $9.28 Million for CAR T Cell Immunotherapy Clinical Trial for Patients with HER2-Positive Breast Cancer That Has Spread to the Brain

Paul Priceman, Ph.D., City of Hope assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation, and his research team have received a $9.28 million award from the California Institute for Regenerative Medicine to support a chimeric antigen receptor (CAR) T cell Phase I clinical trial for the treatment of women with HER2-positive breast cancer that has spread to the brain. [City of Hope] Press Release

Researcher Receives $1.35M Department of Defense Grant for Breast Metastasis Study

Rahul Jandial, M.D., Ph.D., associate professor in City of Hope’s Division of Neurosurgery, Department of Surgery, has received the “Breakthrough” award and a $1.35 million grant from the Department of Defense Breast Cancer Research Program to support his laboratory research into leptomeningeal disease. [City of Hope] Press Release

More Than 700 German Research Institutions Strike Open-Access Deal with Springer Nature

A consortium of more than 700 German research institutions and libraries announced an agreement with publisher Springer Nature to make it simpler for authors to publish their papers open access. The agreement is the largest national open-access deal to date, but it doesn’t allow authors to publish open access in Nature or its sister journals. [ScienceInsider] Editorial

Huge US Government Study to Offer Genetic Counseling

A US government study that aims to sequence the genomes of one million volunteers will partner with a genetic-counseling company to help participants understand their results. It will be the largest US government study to provide such a service. [Nature News] Editorial

As Brexit Nears, Britain’s Drugs, Devices and Pricing Regulators Seek the Exit

Firm details on exactly how the UK will regulate new medicines is still to be decided after it leaves the EU later this year (caveats on timing abound), but we now know that the regulator won’t be run by Dr. Ian Hudson, who is stepping down after six years in charge. [FierceBiotech] Editorial

NEW Cell Death in Immunity and Inflamation
October 6-9, 2019
Crete, Greece

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

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Bioinformatician – Breast Cancer (Royal College of Surgeons)

Postdoctoral Fellow – 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)

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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