Mammary Cell News Volume 10.20 | May 24 2018

TOP STORY

Early Lineage Segregation of Multipotent Embryonic Mammary Gland Progenitors

Molecular profiling and single cell RNA-seq revealed that embryonic multipotent progenitors expressed a unique hybrid basal and luminal signature and the factors associated with the different lineages. Sustained p63 expression in embryonic multipotent progenitors promoted unipotent basal cell fate and was sufficient to reprogram adult luminal cells into basal cells by promoting an intermediate hybrid multipotent-like state. [Nat Cell Biol] Abstract | Press Release

(Ranked by impact factor of the journal)

Clonal Analysis of Notch1-Expressing Cells Reveals the Existence of Unipotent Stem Cells That Retain Long-Term Plasticity in the Embryonic Mammary Gland

The authors found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. [Nat Cell Biol] Abstract

Autophagy Promotes the Survival of Dormant Breast Cancer Cells and Metastatic Tumor Recurrence

Pharmacologic or genetic inhibition of autophagy in dormant breast cancer (BC) cells resulted in significantly decreased cell survival and metastatic burden in mouse and human 3D in vitro and in vivo preclinical models of dormancy. Mechanistically, inhibition of the autophagic flux in dormant BC cells lead to the accumulation of damaged mitochondria and reactive oxygen species, resulting in cell apoptosis. [Nat Commun] Full Article | Press Release

TAK1 Mediates Microenvironment-Triggered Autocrine Signals and Promotes Triple-Negative Breast Cancer Lung Metastasis

Following co-culturing with macrophages or fibroblasts, triple-negative breast cancer cells expressed interleukin-1 (IL1) or tumor necrosis factor-α, respectively. Compared to transforming growth factor-β1-activated kinase-1 (TAK1) inhibition, suppressing IL1 signaling with recombinant IL1 receptor antagonist was less efficient in reducing lung metastasis, possibly due to the additional TAK1 signals coming from distinct stromal cells. [Nat Commun] Full Article | Press Release

Integration of Ca²⁺ Signaling Regulates the Breast Tumor Cell Response to Simvastatin and Doxorubicin

Investigators revealed that both simvastatin and doxorubicin triggered persistent cytosolic Ca²⁺ release, thereby stimulating the proapoptotic BIM pathway and mitochondrial Ca²⁺ overload, which are responsible for metabolic dysfunction and apoptosis induction. Simvastatin and doxorubicin suppressed the prosurvival ERK1/2 pathway in a Ca²⁺-independent and Ca²⁺-dependent manner, respectively. [Oncogene] Full Article

αE-Catenin Is a Candidate Tumor Suppressor for the Development of E-cadherin Expressing Lobular-Type Breast Cancer

Researchers found that inactivating somatic CTNNA1 mutations in human breast cancer correlated with lobular and mixed ducto-lobular phenotypes. Inducible loss of α-catenin in mouse and human E-cadherin expressing breast cancer cells led to atypical localization of E-cadherin, a rounded cell morphology and anoikis resistance. [J Pathol] Abstract

SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4⁺ T Lymphocytes

SV-BR-1-GM cells expressed major histocompatibility complex class II genes (HLA-DRA, HLA-DRB3, HLA-DMA, HLA-DMB), in addition to several other factors known to play immunostimulatory roles. SV-BR-1-GM cells (which also carry the HLA-DRB3^*01:01 allele) treated with yellow fever virus (YFV) envelope 43-59 peptides reactivated YFV-DRB3^*01:01-specific CD4⁺ T cells. [Front Immunol] Full Article | Press Release

Enhanced Breast Cancer Progression by Mutant p53 Is Inhibited by the Circular RNA circ-Ccnb1

Scientists found that circ-Ccnb1 precipitated p53 in p53 wild-type cells, but instead precipitated Bclaf1 in p53 mutant cells. H2AX served as a bridge, linking the interaction of circ-Ccnb1 and wild-type p53, thus allowing Bclaf1 to bind Bcl2 resulting in cell survival. In the p53 mutant cells, circ-Ccnb1 formed a complex with H2AX and Bclaf1, resulting in the induction of cell death. [Cell Death Differ] Full Article

Heat Shock Factor 1 Confers Resistance to Lapatinib in ERBB2-Positive Breast Cancer Cells

The authors found that multiple adaptive receptor tyrosine kinases are activated in lapatinib-resistant cells in vivo, some of which have been previously described (Axl, MET) and some of which were novel (PDGFRα, PDGFRβ, VEGFR1, MUSK, NFGR). All lapatinib-resistant cells showed chronically activated HSF1 and its transcriptional targets, heat shock proteins, and, as a result, superior tolerance to proteotoxic stress. [Cell Death Dis] Full Article

Autophagy, Cell Viability and Chemo-Resistance Are Regulated by miR-489 in Breast Cancer

Researchers identified autophagy as a novel pathway targeted by miR-489 and reported Unc-51 like autophagy activating kinase 1 and lysosomal protein transmembrane 4 beta (LAPTM4B) to be direct targets of miR-489. They demonstrated autophagy inhibition and LAPTM4B down-regulation as a major mechanism responsible for miR-489-mediated doxorubicin sensitization. [Mol Cancer Res] Abstract

Transcriptomic Response of Breast Cancer Cells to Anacardic Acid

In MCF-7 cells, 80 anacardic acid (AnAc)-responsive genes were identified, including lncRNA MIR22HG. More AnAc-responsive genes (886) were identified in MDA-MB-231 cells. Only six genes were commonly altered by AnAc in both cell lines: SCD, INSIG1, and TGM2 were decreased and PDK4, GPR176, and ZBT20 were increased. [Sci Rep] Full Article

Estrogen Receptor-Negative Progesterone Receptor-Positive Breast Cancer – “Nobody’s Land” or Just an Artifact?

Researchers present background theories on the estrogen receptor(−)/progesterone receptor(+) breast cancer origin and their epidemiological and clinicopathological characteristics, including the predictive and prognostic significance of these rare tumors. [Cancer Treat Rev] Abstract

Visit our reviews page to see a complete list of reviews in the mammary cell research field.

Institut Curie Names Intel Lead Partner to Implement High-Performance Computing and Artificial Intelligence in Accelerating Genome Sequencing and Interpretation for Oncology

Institut Curie and Intel initiate a pioneering collaboration to develop, use and implement innovative bioinformatics tools, pipelines and techniques to improve the use of molecular profiling across both research and clinical oncology settings. [Institut Curie] Press Release

TEDCO Announces $7.1 Million in New Stem Cell Program Awards

The Maryland Stem Cell Research Commission has approved funding for 25 awards for a total of $7,140,901. Established by the Governor and the Maryland General Assembly through the Maryland Stem Cell Research Act of 2006, the Maryland Stem Cell Research Fund promotes state-funded stem cell research and cures through grants to both public and private entities in Maryland. [TEDCO] Press Release

AstraZeneca Opens South San Francisco Facility Housing 400 R&D Staff

AstraZeneca (AZ) has officially opened its new research facility in South San Francisco, bundling five of its Bay Area sites into a single unit at the heart of California’s biotech cluster. The new location—at the Cove at Oyster Point—is the new workplace for around 400 employees gathered from AZ’s Technology Innovation & Delivery Excellence unit, as well as subsidiaries Acerta Pharma, MedImmune, and Pearl Therapeutics. [FierceBiotech] Press Release

FDA Plans to Speed Path to Approval for Some Gene Therapies, Starting with Hemophilia

The FDA will soon be alerting companies that certain gene therapies in development can qualify for less arduous review at the agency. Gottlieb said that hemophilia is the first disease the FDA will target with its new policy. [STAT News] Editorial

PM Will Pay to Have ‘Full Association’ with EU Research

The Prime Minister made the strongest commitment yet to “fully associate” the UK with the EU’s £68bn research program post-Brexit. Theresa May said the UK would be willing to make “an appropriate contribution” and in return it would expect a “suitable level of influence”. [BBC News] Editorial

Science Needs Clarity on Europe’s Data-Protection Law

As a commendable European law on personal data comes into force, the research community must not let excessive caution about data sharing, however understandable, become the default position. [Nature News] Editorial

Indonesian Plan to Clamp Down on Foreign Scientists Draws Protest

The government’s proposals include stricter rules, and tougher penalties for researchers who break existing ones. [Nature News] Editorial

NEW The New York Stem Cell Foundation (NYSCF) Conference
October 23-24, 2018
New York, New York, United States

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

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

NEW Postdoctoral Position – Breast Cancer Research (Northwestern University)

Postdoctoral Posion – Basic & Translational Breast Cancer Research (Northwestern University)

Researcher Positions – Genome Directed Cancer Therapy (University of Bergen)

Postdoctoral Position – Genome Directed Cancer Therapy (University of Bergen)

Postdoctoral Positions – Translational Bioinformatics or Molecular Cancer Biology (University of Pittsburgh Cancer Institute)

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

Postdoctoral Position – Breast Cancer Research (Rutgers Cancer Institute of New Jersey)

Graduate Student – Breast and Colorectal Cancer (Dalhousie University)

Postdoctoral Fellows – Breast Cancer Stem Cell Research (New York University School of Medicine)

Postdoctoral Fellow or Research Scientist – Breast Cancer Research (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellowship – Cancer Research (Mass General Hospital/Harvard Medical School)

Postdoctoral Fellow – Breast Cancer Research (Northwestern University)

Postdoctoral Researcher – Breast Cancer (Baylor College of Medicine)

Senior Research Technician – Breast Cancer (Baylor College of Medicine)

Research Technician – Breast Cancer (Baylor College of Medicine)

Postdoctoral Fellow – Cancer Research (Indiana Uniersity School of Medicine)

Postdoctoral Fellows – Molecular and Translational Cancer Biology (Thomas Jefferson University)

Postdoctoral Researcher – Breast Cancer (UT Southwestern Medical Center)

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