Mammary Cell News Volume 7.36 | Sep 17 2015

PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer
The authors showed that primary breast cancer cells display extensive metabolic heterogeneity and engage distinct metabolic programs depending on their site of metastasis. [Cell Metab] Abstract | Graphical Abstract

In Vivo Capture and Label-Free Detection of Early Metastatic Cells
Scientists report a method for the early detection of metastasis using an implanted scaffold to recruit and capture metastatic cells in vivo, which achieves high cell densities and reduces the tumor burden within solid organs ten-fold. [Nat Commun] Abstract | Press Release

Ligand-Dependent Genomic Function of Glucocorticoid Receptor in Triple-Negative Breast Cancer
Researchers found that dexamethasone-regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Also, these glucocorticoids-regulated genes are aberrantly expressed in TNBC patients and are associated with unfavourable clinical outcomes. [Nat Commun] Full Article

Breast Cancer Dissemination Promoted by a Neuregulin-Collagenase 3 Signaling Node
Investigators showed that the ErbB ligands, Neuregulins (NRGs), promote metastatic dissemination of breast cancer cells by switching on a kinase-metalloproteinase network. Genomic, biochemical and functional studies identified matrix metalloproteinases, particularly stromelysin 2 and collagenase 3, as key mediators of the NRG-induced dissemination properties of breast cancer cells. [Oncogene] Abstract

Neddylation Controls Basal MKK7 Kinase Activity in Breast Cancer Cells
Scientists report that the inhibition of ubiquitination-like post-translational modification neddylation through different strategies results in enhanced basal c-Jun NH2-terminal protein kinase phosphorylation in human breast cancer cells. [Oncogene] Abstract

LncRNA HOTAIR Enhances ER Signaling and Confers Tamoxifen Resistance in Breast Cancer
Researchers found that HOTAIR (HOX antisense intergenic RNA) overexpression increases breast cancer cell proliferation, whereas its depletion significantly impairs cell survival and abolishes tamoxifen-resistant cell growth. [Oncogene] Abstract

Disabling of the erbB Pathway Followed by IFN-γ Modifies Phenotype and Enhances Genotoxic Eradication of Breast Tumors
Reversion of the malignant phenotype of erbB2-transformed cells can be driven by anti-erbB2/neu monoclonal antibodies (mAbs), which disrupt the receptor’s kinase activity. The authors examined the biologic effects of IFN-γ alone or after anti-erbB2/neu mAb treatment of erbB2-positive cells. [Cell Rep]
Full Article | Graphical Abstract

SRSF3 and hnRNP H1 Regulate a Splicing Hotspot of HER2 in Breast Cancer Cells
Investigators look at the expression and regulation of a group of HER2 splice variants produced by a splicing hotspot. Knockdown of SRSF3 resulted in a switch from the oncogenic Δ16HER2 to p100 which inhibits cell proliferation. [RNA Biol] Abstract

The β-Catenin Signaling Pathway Induces Aggressive Potential in Breast Cancer by Up-Regulating the Chemokine CCL5
Researchers examined whether deregulation of β-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of β-catenin revealed a higher level of CCL5 expression. [Exp Cell Res] Abstract

Alteration of Gene Expression in MDA-MB-453 Breast Cancer Cell Line in Response to Continous Exposure to Trastuzumab
Investigators researched the alteration in gene expression in response to Trastuzumab resistance after long-term exposure to Trastuzumab. The Trastuzumab-resistant MDA-MB-453 cell line was developed by exposing cells to 10 μM Trastuzumab continuously for six months. [Gene] Abstract

CLINICAL RESEARCH

Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study
The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a Phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor–positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg or anastrozole 1 mg. [J Clin Oncol] Full Article

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER⁺ Breast Cancer When Administered Using Intermittent or Continuous Schedules
AZD2014 is a small molecule ATP competitive inhibitor of mammalian target of rapamycin (mTOR) which inhibits both mTORC1 and mTORC2 complexes and has a greater inhibitory function against mTORC1 than the clinically approved rapalogues. Female patients with advanced breast cancer were given lapatinib once daily in 28-day cycles with gemcitabine administered on day 1, 8 and 15. [Invest New Drugs] Abstract | Full Article

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Cancer Research UK and MedImmune Launch Ground-Breaking Biotherapeutics Research Center in Cambridge
A new laboratory that will focus on the discovery and development of novel biologic cancer treatments and diagnostics has been opened this week in Cambridge. The state-of-the-art CRUK-MEDI Alliance Laboratory is an innovative collaboration between Cancer Research UK, its commercial arm Cancer Research Technology, and MedImmune, the global biologics research and development arm of AstraZeneca. [Cancer Research UK] Press Release

Mayo Clinic Receives Large Federal Grant to Fund Clinical Test of Innovative Triple-Negative Breast Cancer Vaccine
Researchers on Mayo Clinic’s Florida campus have been awarded a $13.3 million, five-year federal grant to test a vaccine designed to prevent the recurrence of triple-negative breast cancer, a subset of breast cancer for which now there are no targeted therapies. [Mayo Clinic] Press Release | Video

Waltz Receives VA Merit Grant for Continuing Breast Cancer Research
Susan Waltz, PhD, professor in the Department of Cancer Biology and member of both the Cincinnati Cancer Center and University of Cincinnati Cancer Institute, received a U.S. Department of Veterans Affairs (VA) Merit Grant, totaling over $1 million over the next four years, to continue research on the function of the Ron receptor tyrosine kinase in breast cancer. [University of Cincinnati Cancer Center] Press Release

Geneticist Mary-Claire King to Receive Lasker Foundation Award
The University of Washington and UW Medicine announced that Mary-Claire King, UW Professor of Medicine, will receive the 2014 Lasker-Koshland Special Achievement Award in Medical Science. She was the first to demonstrate that a genetic predisposition for breast cancer exists, as the result of inherited mutations in the gene she named BRCA1. [University of Washington] Press Release

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NEW Research Scientist – Epithelial Stem Cells (A*STAR)

Postdoctoral Research Associate – Breast Cancer Invasion / Extracellular Matrix / Proteomics / Microscopy (University of Liverpool)

Postdoctoral Researcher – Epigenetic Modifiers (Van Andel Research Institute)

Postdoctoral Fellowship – Cancer Biology (Massachusetts General Hospital Cancer Center/Harvard Medical School)

Postdoctoral Research Fellow – Metastatic Breast Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Proteomic, Glycomic and Autoantibody Biomarkers of Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cancer Biology (National Cancer Institute)

Postdoctoral Position – Cancer Biology (Northwestern University)

Postdoctoral Position – Inflammation & Breast Tumor Metastasis (Stephenson Cancer Center)

Postdoctoral Research Fellow (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Associate – Breast Stem Cell Biology (University of Miami Miller School of Medicine)

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