Mammary Cell News Volume 10.27 | Jul 12 2018

TOP STORY

Discovery of Selective Estrogen Receptor Covalent Antagonists (SERCAs) for the Treatment of ERa(WT) and ERa(MUT) Breast Cancer

Scientists identified H3B-5942 which covalently inactivates both wild-type (WT) and mutant (MUT) estrogen receptor alpha (ERa) by targeting Cys530 and enforcing a unique antagonist conformation. In vitro comparisons of H3B-5942 with standard of care and experimental agents confirmed increased antagonist activity across a panel of ERa(WT) and ERa(MUT) cell lines. [Cancer Discov] Abstract | Press Release

(Ranked by impact factor of the journal)

Traceable Bioinspired Nanoparticle for the Treatment of Metastatic Breast Cancer via NIR‐Trigged Intracellular Delivery of Methylene Blue and Cisplatin

A cytotoxic T lymphocyte (CTL)‐inspired nanovesicle with a cell membrane-derived shell and a methylene blue (MB) and cisplatin (Pt) loaded gelatin nanogel core was created. It released MB and Pt, and then delivered them into the cytosol of cancer cells, which could be visualized by imaging the recovery of MB‐derived fluorescence. [Adv Mater] Abstract

Enhanced Intracellular Ca²⁺ Nanogenerator for Tumor-Specific Synergistic Therapy via Disruption of Mitochondrial Ca²⁺ Homeostasis and Photothermal Therapy

Researchers showed that dual enhanced Ca²⁺ nanogenerator (DECaNG) could produce a large amount of Ca²⁺ directly and persistently to flow to mitochondria, leading to upregulation of Caspase-3, cytochrome c, and downregulation of Bcl-2 and ATP followed by cell apoptosis. [ACS Nano] Abstract | Graphical Abstract

Fibronectin Rescues Estrogen Receptor α from Lysosomal Degradation in Breast Cancer Cells

Investigators showed that estrogen drove membrane estrogen receptor α into endosomes in breast cancer cells and that its fate was determined by the presence of fibronectin (FN) in the extracellular matrix; it was trafficked to lysosomes in the absence of FN and avoided the lysosomal compartment in its presence. [J Cell Biol] Full Article | Press Release

Estrogen-Regulated Feedback Loop Limits the Efficacy of Estrogen Receptor-Targeted Breast Cancer Therapy

The authors identified C-terminal SRC kinase (CSK) as a critical node in a previously unappreciated negative feedback loop that limits the efficacy of current estrogen-receptor (ER)-targeted therapies. Estrogen directly drove CSK expression in ER positive breast cancer. [Proc Natl Acad Sci USA] Full Article

LINC01638 lncRNA Activates MTDH-Twist1 Signaling by Preventing SPOP-Mediated c-Myc Degradation in Triple-Negative Breast Cancer

LINC01638 maintained the mesenchymal traits of triple-negative breast cancer cells, including an enriched epithelial-mesenchymal transition signature and cancer stem cell-like state. LINC01638 knockdown suppressed tumor proliferation and metastasis both in vitro and in vivo. LINC01638 interacted with c-Myc to prevent SPOP-mediated c-Myc ubiquitination and degradation. [Oncogene] Abstract

Nuclear Respiratory Factor 1 Promotes Spheroid Survival and Mesenchymal Transition in Mammary Epithelial Cells

Nuclear respiratory factor 1 (NRF1)-promoted spheroid survival was linked to its stimulation of mitochondrial OXPHOS, cell migration, invasion, and mesenchymal transition. Conversely, NRF1 knockdown in breast cancer MDA-MB-231 cells reduced spheroids, migration, invasion, and mesenchymal marker expression. [Oncogene] Abstract

SREBP1, Targeted by miR-18a-5p, Modulates Epithelial-Mesenchymal Transition in Breast Cancer via Forming a Co-Repressor Complex with Snail and HDAC1/2

Scientists identified sterol regulatory element binding transcription protein 1 (SREBP1), the master transcription factor that controls lipid metabolism, as a candidate target of miR-18a-5p. SREBP1 was overexpressed and strongly associated with worse clinical outcomes in breast cancer. Functionally SREBP1 promoted growth and metastasis of breast cancer both in vitro and in vivo. [Cell Death Differ] Abstract

Abiraterone Shows Alternate Activity in Models of Endocrine Resistant and Sensitive Disease

Abiraterone showed paradoxical impact on proliferation by stimulating cell growth or death, depending on whether the cells were hormone-dependent or had undergone prolonged estrogen-deprivation, respectively. Abiraterone increased estrogen-receptor (ER)-turnover, induced ER-mediated transactivation and ER-degradation via the proteasome. [Br J Cancer] Full Article

α-Ketoglutarate Dehydrogenase Inhibition Counteracts Breast Cancer-Associated Lung Metastasis

α-ketoglutarate dehydrogenase inhibitor, (S)-2-[(2,6-dichlorobenzoyl) amino] succinic acid (AA6) altered the krebs cycle causing intracellular α-ketoglutarate (α-KG) accumulation. Treatment with AA6 determined an α-KG accumulation paralleled by an enhanced production of nitric oxide. This epigenetically remodelled metabolic environment efficiently counteracted the initiating steps of tumor invasion inhibiting the epithelial-to-mesenchymal transition. [Cell Death Dis] Full Article

Senescent Tumor Cells Building Three-Dimensional Tumor Clusters

Senescent cells in a dense mono-layer of breast cancer colony acted as aggregating centers for non-senescent cells in their vicinity. The senescent cells actively formed localized 3D cell-clusters in a confluent 2D tumor layer. The biophysical mechanism underpinning the surprising phenomenon primarily involved mitotic cell-rounding, dynamic and differential cell attachments, and cellular chemotaxis. [Sci Rep] Full Article

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HOXA11 Antisense Long Noncoding RNA (HOXA11-AS): A Promising lncRNA in Human Cancers

The authors summarize the advanced research progression concerning the expression and role of HOXA11‐AS in different human malignancies. Functional HOXA11‐AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11‐AS‐targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers. [Cancer Med] Full Article

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Anti-PD-L1 Immunotherapy Plus ABRAXANE^® Significantly Reduced the Risk of Disease Worsening or Death in Patients with Metastatic or Locally Advanced Triple Negative Breast Cancer in Phase III IMpassion130 Study

Celgene Corporation announced that the Phase III IMpassion130 study, met its co-primary endpoint of progression-free survival. [Celgene Corporation] Press Release

New Preclinical Results on Onxeo’s AsiDNA^™, First-in-Class DNA Repair Inhibitor, Point to Strong Synergy and Reversion of Tumor Resistance when Combined to PARP Inhibitors

Onxeo S.A. announced new positive results from preclinical studies of AsiDNA^™, its first-in-class DNA Repair inhibitor, in combination with PARP inhibitors. [Onxeo] Press Release

It’s Time to Burst the Biomedical Bubble in UK Research

A new study calls for a rebalancing of research and innovation funding to better meet the UK’s economic, social and health needs. [The Guardian] Editorial

Petition Asks AAAS to Remove Fellows with Sexual Harassment Records

A petition by members of the scientific community asks the American Association for the Advancement of Science (AAAS) to remove fellows who have been found guilty of sexual harassment or assault. [The Scientist] Editorial

Chinese Researchers to Get More Autonomy Over Lab Spending

Chinese Premier Li Keqiang says the country will ease restrictive rules governing how research funds are used, and cut red tape for researchers. Revised rules are designed to help researchers focus on their work and compete with their counterparts globally. [Nature News] Editorial

UK Universities Fall Short on Reporting Misconduct Investigations

The United Kingdom should establish a committee to monitor efforts by the nation’s universities to properly conduct misconduct investigations, a parliamentary inquiry recommends. The guidance follows a new report released on 11 July, revealing that one in four UK universities does not comply with research integrity guidelines released six years ago. [Nature News] Editorial

NEW Cell Symposia: Translation of Stem Cells to the Clinic: Challenges and Opportunities
December 2-4, 2018
Los Angeles, California, United States

Visit our events page to see a complete list of events in the community.

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

NEW Postdoctoral Research Scientist – DNA Repair Assay, Breast Cancer (Columbia Center for Radiological Research)

Postdoctoral Position – Breast Cancer (University of Trento)

Clinical Research Scientist – Oncology Medical Affairs Breast Cancer (Lilly)

Instructor or Assistant Professor – Breast and Colon Cancer Metastasis Research (Louisiana State University Health Sciences Center)

Cancer Faculty Investigators – Basic & Translational Cancer Research (The University of Alabama)

Postdoctoral Fellow – Molecular Mechanisms of Breast & Colon Cancers (Dalhousie University)

Post-doctoral Fellow – Ovarian and Breast Cancers (John Hopkins University)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University Feinberg School of Medicine)

Postdoctoral Research Associate – Breast Cancer (Howard University)

Postdoctoral Fellow – Breast & Ovarian Cancer Genomics (University of Texas Health Science Center at Houston)

Cancer Scientists – Breast Cancer Research (Qatar Biomedical Research Institute)

Postdoctoral Position – Ovarian and Breast Cancer Research (Indiana University School of Medicine)

Postdoctoral Research Fellow – Translational Mitochondrial Research (Fred Hutch Cancer Research Center)

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