Mammary Cell News Volume 6.42 | Oct 30 2014

ASPP2 Controls Epithelial Plasticity and Inhibits Metastasis through ​β-Catenin-Dependent Regulation of ​ZEB1
Scientists identified ​ASPP2, a haploinsufficient tumor suppressor, ​p53 activator and ​PAR3 binding partner, as a molecular switch of mesenchymal to epithelial transition and epithelial to mesenchymal transition. ​
[Nat Cell Biol] Abstract | Press Release

Hypoxia Promotes Stem Cell Phenotypes and Poor Prognosis through Epigenetic Regulation of ​DICER
Researchers identified tumor hypoxia as a regulator of ​DICER expression in large cohorts of breast cancer patients. Reduced microRNA processing leads to derepression of the miR-200 target ​ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. [Nat Commun] Abstract | Press Release

Cytokeratin19 Induced by HER2/ERK Binds and Stabilizes HER2 on Cell Membranes
Using an LC-MS/MS proteomics approach, investigators found that cytokeratin19 (KRT19) was upregulated in HER2-overexpressing cells and tissues. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. [Cell Death Differ] Abstract

MYC Regulates the Unfolded Protein Response and Glucose and Glutamine Uptake in Endocrine Resistant Breast Cancer
Scientists identified MYC, an oncoprotein that is upregulated in endocrine resistant breast cancer, as a regulator of the unfolded protein response in glucose-deprived conditions. ER⁺ human breast cancer cell lines and rat mammary tumors were used to confirm upregulation of MYC in endocrine resistance. [Mol Cancer] Full Article

Human Breast Progenitor Cell Numbers Are Regulated by WNT and TBX3
Researchers identified two phenotypically distinguishable lineage-committed progenitor cells that contribute to different structural elements and are regulated via hormonal and non-hormonal mechanisms. WNT signaling regulates both types of progenitor activity. [PLoS One] Full Article

Elevated CXCL1 Expression in Breast Cancer Stroma Predicts Poor Prognosis and Is Inversely Associated with Expression of TGF-Beta Signaling Proteins
Researchers sought to characterize the expression patterns of CXCL1 in breast cancer stroma, determine the prognostic significance of stromal CXCL1 expression, and identify factors affecting stromal CXCL1 expression. [BMC Cancer] Abstract | Full Article

Bmi1 Regulates Self-Renewal and Epithelial to Mesenchymal Transition in Breast Cancer Cells through Nanog
Scientists explored the role of Bmi1 in regulating the stemness and drug resistance of breast cancer cells. Bmi1 overexpression in immortalized and transformed breast epithelial cells increased their sphere-forming efficiency, induced epithelial to mesenchymal transition with an increase in the expression of stemness-related genes. [BMC Cancer] Abstract | Full Article

CLINICAL RESEARCH

Biomarker Analyses in CLEOPATRA: A Phase III, Placebo-Controlled Study of Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive, First-Line Metastatic Breast Cancer
Investigators explored the prognostic and/or predictive value of human epidermal growth factor receptor 2 (HER2) pathway-related biomarkers in the Phase III study of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel as first-line treatment for patients with HER2-positive metastatic breast cancer. [J Clin Oncol] Abstract

Phase III Study of Iniparib Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin in Patients With Metastatic Triple-Negative Breast Cancer
A randomized Phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib over gemcitabine and carboplatin in clinical benefit rate, response rate, progression-free survival, and overall survival. Scientists formally compared the efficacy of these regimens in a Phase III trial. [J Clin Oncol] Abstract

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Bristol-Myers Squibb Enters into Agreement that Provides an Exclusive Option to Acquire F-star Alpha Ltd. and Its Novel HER2-Targeted Therapy
Bristol-Myers Squibb Company and F-star Alpha Ltd. have entered into an agreement that provides Bristol-Myers Squibb the exclusive option to acquire F-star Alpha Ltd. and gain worldwide rights to its lead asset FS102. FS102 is a novel Phase I ready human epidermal growth factor receptor 2 (HER2)-targeted therapy in development for the treatment of breast and gastric cancer among a well-defined population of HER2-positive patients who do not respond or become resistant to current therapies. [Bristol-Myers Squibb Company] Press Release

Compugen Discloses Successful Validation Results for Novel B7/CD28-Like Cancer Immunotherapy Target Candidate
Compugen Ltd. disclosed successful experimental data for CGEN-15027, a Compugen-discovered immune checkpoint target candidate. The experimental results include its expression in the cancer microenvironment, both on cancer cells derived from lung, breast, and liver cancer patients, and on tumor infiltrating immune cells. [Compugen Ltd.] Press Release

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NEW Postdoctoral Position – Protein-Protein Interactions in Leukemia and Breast Cancer (University of Dundee)

PhD Position – Protein Interactions in Cancer Regulation (University of East Anglia)

Postdoctoral Position – Novel DNA Damage Checkpoint Pathways and Variants in Potential Breast Cancer Genes (University of Copenhagen)

Postdoctoral Fellow – Breast Cancer (University of Texas Health Science Center at San Antonio)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

Postdoctoral Position – Breast Cancer Biology (UT Southwestern)

Postdoctoral Fellow – Breast Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Stem Cells and Breast Cancer (Albert Einstein College of Medicine)

Postdoctoral Fellow – Breast Cancer Translational Research (University of Houston – College of Pharmacy)

Scientist – Mammary Cell Research (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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