Mammary Cell News Volume 11.35 | Sep 12 2019

TOP STORY

Mitochondrial Supercomplex Assembly Promotes Breast and Endometrial Tumorigenesis by Metabolic Alterations and Enhanced Hypoxia Tolerance

Scientists demonstrated that COX7RP overexpression in breast and endometrial cancer cells promoted in vitro and in vivo growth, stabilized mitochondrial supercomplex assembly even in hypoxic states, and increased hypoxia tolerance. Metabolomic analyses revealed that COX7RP overexpression modulated the metabolic profile of cancer cells, particularly the steady-state levels of tricarboxylic acid cycle intermediates. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Intracellular Redox Potential Is Correlated with miRNA Expression in MCF7 Cells under Hypoxic Conditions

Researchers demonstrated a correlation between intracellular redox potential and the concentrations of miRNAa involved in the cells’ response to changes in oxygen pressure. The correlations were established using surprisal analysis. [Proc Natl Acad Sci USA] Abstract

A pH-Sensitive Nanotherapeutic System Based on a Marine Sulfated Polysaccharide for the Treatment of Metastatic Breast Cancer through Combining Chemotherapy and COX-2 Inhibition

Investigators designed a pH-sensitive nanotherapeutic system based on propylene glycol alginate sodium sulfate (PSS), a marine sulfated polysaccharide that possesses anti-platelet aggregation activity and has been used as a heparinoid drug in China. A facile one-pot nanoprecipitation method was used to prepare this nanotherapeutic system named as PSS@DC nanoparticles, in which DOX and CXB were complexed to form hydrophobic nanocores and PPS coated these nanocores through conjugation with DOX via a highly acid-labile benzoic-imine linker. [Acta Biomater] Full Article | Graphical Abstract

Mitochondrial Fragmentation, Elevated Mitochondrial Superoxide and Respiratory Supercomplexes Disassembly Is Connected with the Tamoxifen-Resistant Phenotype of Breast Cancer Cells

The authors showed that Tam5R cells exhibited a significant decrease in mitochondrial respiration, low abundance of assembled mitochondrial respiratory supercomplexes, a more fragmented mitochondrial network connected with DRP1 Ser637 phosphorylation, higher glycolysis and sensitivity to 2-deoxyglucose. [Free Radic Biol Med] Full Article | Graphical Abstract

Protease Nexin I Is a Feedback Regulator of EGF/PKC/MAPK/EGR1 Signaling in Breast Cancer Cells Metastasis and Stemness

Researchers found that protease nexin-1 (PN-1) was up-regulated in breast cancer, which promoted cell invasion, migration and stemness. Furthermore, by using specific inhibitors, they discovered that epidermal growth factor (EGF) up-regulated PN-1 in breast cancer cells through cascade activation of epidermal growth factor receptor to the activation of protein kinase Cδ, mitogen-activated protein kinase and extracellular signal-related kinase, which finally led to the up-regulation of early growth response protein 1. [Cell Death Dis] Full Article

Intrinsic Adriamycin Resistance in p53-Mutated Breast Cancer Is Related to the miR-30c/FANCF/REV1-Mediated DNA Damage Response

Investigators report that breast cancer (BrCa) cells expressing mutp53 were more resistant to adriamycin than cells with wild-type p53. The DNA repair protein Fanconi anemia complementation group F protein and the translesion synthesis DNA polymerase REV1 protein was frequently abundant in the context of mutant p53 of BrCa. [Cell Death Dis] Full Article

Development of Therapeutic Anti-JAGGED1 Antibodies for Cancer Therapy

Scientists report the development and characterization of human/rat-specific JAG1-neutralizing monoclonal antibodies. Epitope mapping identified their binding to the Notch receptor interaction site within the JAG1 Delta/Serrate/Lag2 domain, where E228D substitution prevented effective binding to the murine Jag1 orthologue. [Mol Cancer Ther] Abstract | Full Article

miRNA-Dependent Regulation of STIM1 Expression in Breast Cancer

The authors showed that STIM1 expression was regulated post-transcriptionally by the miRNA machinery and identified miR-223 and miR-0150 as regulators of STIM1 expression in the luminal non-aggressive MCF7 breast cancer cell line. In contrast, STIM1 expression in the more aggressive basal triple-negative MDA-MB-231 cell line was not significantly modulated by a single miRNA species but was rather upregulated due to inhibition of the miRNA machinery through downregulation of Ago2. [Sci Rep] Full Article

Overexpression and Alternative Splicing of NF-YA in Breast Cancer

Researchers focused on breast carcinomas, and analyzed RNA-Seq datasets of TCGA and 54 BRCA cell lines at gene and isoforms level. They partitioned all tumors in the four major subclasses. NF-YA, but not histone-fold subunits NF-YB/NF-YC, was globally overexpressed, correlating with the proliferative Ki67 marker and a common set of 840 genes, with cell-cycle, metabolism GO terms. [Sci Rep] Full Article

Ouabain Impairs Cancer Metabolism and Activates AMPK-Src Signaling Pathway in Human Cancer Cell Lines

Investigators showed that treatment with ouabain caused simultaneous activation of AMPK and Src signaling pathways in human lung cancer A549 cells and human breast cancer MCF7 cells. Co-treatment with AMPK inhibitor compound C or siRNA greatly abrogated ouabain-induced Src activation, whereas co-treatment with Src inhibitor PP2 had little effect on ouabain-induced AMPK activity, suggesting that AMPK served as an upstream regulator of the Src signaling pathway. [Acta Pharmacol Sin] Abstract

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Cancer-Associated Adipocytes: Key Players in Breast Cancer Progression

Scientists focus on the potential mechanisms involved with special attention to the adipocyte-cancer cell circle in breast cancer. They envisage that besides having a direct impact on tumor cells, cancer-associated adipocytes systemically preconditions the tumor microenvironment by favoring anti-tumor immunity. [J Hematol Oncol] Full Article

Panoptic View of Prognostic Models for Personalized Breast Cancer Management

The authors summarize the prognostic and predictive insights provided by commercially available gene expression-based tests and other multivariate or clinical -omics-based prognostic/predictive models currently under development, and proposes a more inclusive multiplatform approach to tackling the challenging heterogeneity of breast cancer to individualize its management. [Cancers] Full Article

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Cyclacel Pharmaceuticals Announces First Patient Treated with Oral CYC065 in a Phase I Study in Patients with Advanced Solid Tumors

Cyclacel Pharmaceuticals, Inc. announced treatment of the first patient with an oral formulation of CYC065, a CDK2/9 inhibitor, in part 3 of a Phase I study which is evaluating single agent CYC065 in patients with advanced solid cancers. Parts 1 and 2 of the study are evaluating CYC065 administered as an intravenous infusion. [Cyclacel Pharmaceuticals, Inc.] Press Release

Daiichi Sankyo Advances [Fam-] Trastuzumab Deruxtecan (DS-8201) in Japan with Regulatory Submission in HER2 Positive Metastatic Breast Cancer

Daiichi Sankyo Company, Limited announced the submission of a New Drug Application to Japan’s Ministry of Health, Labour and Welfare for the use of [fam-] trastuzumab deruxtecan, an investigational HER2 targeting antibody drug conjugate, for the treatment of patients with HER2 positive metastatic breast cancer. [Daiichi Sankyo Company] Press Release

Laskers Go to Immunologists, Developers of Breast Cancer Therapy

The 2019 Lasker-DeBakey Clinical Medical Research Award goes to H. Michael Shepard, formerly of Genentech, Dennis Slamon of the University of California, Los Angeles, and Axel Ullrich of the Max Planck Institute of Biochemistry and formerly of Genentech for the development of a monoclonal antibody therapy called Herceptin that has saved the lives of countless women with breast cancer. [TheScientist] Press Release

Clubby and ‘Disturbing’ Citation Behavior by Researchers in Italy Has Surged

The rate at which scientists in Italy cite themselves and their compatriots is rising faster than in ten other developed countries, according to a new study. The surge in Italy’s clubby citation behavior is likely the result of a 2010 law requiring productivity standards for academic recruitment or promotion, the study authors say. [ScienceInsider] Editorial

EU Research Commissioner Named, but Lacks ‘Research’ in Her Title

Mariya Gabriel, a conservative politician from Bulgaria, is slated to become the next European research chief- although her job title, unlike that of her predecessors, doesn’t include the words “research” or “science.” Some researchers and science policy experts worry the new job title could signal a reduced standing for science within von der Leyen’s proposed executive branch for the European Union, made up of 26 commissioners. [ScienceMagazine] Editorial

US EPA to Eliminate All Mammal Testing by 2035

The US Environmental Protection Agency (EPA) in Washington, DC, announced September 10^th that it will stop conducting or funding studies on mammals by 2035. The move, which is already eliciting strong reactions from groups supporting or opposing experiments on animals, makes EPA the first federal agency to put a hard deadline on phasing out animal research. [Science Magazine] Editorial

NEW Cancer Epigenetics: New Mechanisms and Therapeutic Opportunities
January 26-30, 2020
Keystone, Colorado, United States

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NEW 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)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

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

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

Bioinformatician – Breast Cancer (Royal College of Surgeons in Ireland)

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

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

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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