Mammary Cell News Volume 8.04 | Feb 4 2016

PAF-Wnt Signaling-Induced Cell Plasticity Is Required for Maintenance of Breast Cancer Cell Stemness
Scientists identified PCNA-associated factor (PAF) as a key molecule that controls cancer cell stemness. PAF is highly expressed in breast cancer cells but not in mammary epithelial cells. [Nat Commun] Full Article

CHK2-BRCA1 Tumor-Suppressor Axis Restrains Oncogenic Aurora-A Kinase to Ensure Proper Mitotic Microtubule Assembly
Investigators uncovered a dual molecular mechanism by which the checkpoint kinase 2 (CHK2)-breast cancer type 1 susceptibility protein (BRCA1) axis restrains oncogenic Aurora-A activity during mitosis and identify BRCA1 itself as a target for Aurora-A relevant for chromosomal instability. [Proc Natl Acad Sci USA] Abstract

WASF3 Provides the Conduit to Facilitate Invasion and Metastasis in Breast Cancer Cells through HER2/HER3 Signaling
Researchers showed that WASF3 is present in the HER2 immunocomplex and suppression of WASF3 function leads to suppression of invasion even in the presence of HER2 expression. [Oncogene] Abstract

A Function-Blocking CD47 Antibody Suppresses Stem Cell and EGF Signaling in Triple-Negative Breast Cancer
The authors’ data revealed a novel signal-regulatory protein-α-independent mechanism by which therapeutic CD47 antibodies could control tumor growth by autonomously forcing differentiation of cancer stem cells. [Oncotarget] Full Article

ABL Kinases Promote Breast Cancer Osteolytic Metastasis by Modulating Tumor-Bone Interactions through TAZ and STAT5 Signaling
Scientists report that ABL kinases promoted metastasis of breast cancer cells to bone by regulating the crosstalk between tumor cells and the bone microenvironment. [Sci Signal] Abstract

Intermittent High Dose Scheduling of AZD8835, a Novel Selective Inhibitor of PI3Kα and PI3Kδ, Demonstrates Treatment Strategies for PIK3CA-Dependent Breast Cancers
Scientists report studies with a novel PI3K inhibitor, AZD8835, currently in Phase I clinical evaluation. AZD8835 is a potent inhibitor of PI3Kα and PI3Kδ with selectivity vs. PI3Kβ, PI3Kγ and other kinases that preferentially inhibited growth in cells with mutant PIK3CA status, such as in ER⁺ breast cancer cell lines BT474, MCF7 and T47D. [Mol Cancer Ther] Abstract | Full Article

MicroRNA-101 Targets Von Hippel-Lindau Tumor Suppressor (VHL) to Induce HIF1α Mediated Apoptosis and Cell Cycle Arrest in Normoxia Condition
The authors demonstrated that microRNA-101 (miR-101) was rapidly and transiently induced after hypoxia in breast cancer cells. Over-expression of miR-101 significantly inhibited cell proliferation in breast cancer cells through increased apoptosis and cell cycle arrest in normoxia condition. [Sci Rep] Full Article

A Prognostic Signature Based on Three-Genes Expression in Triple-Negative Breast Tumors with Residual Disease
Researchers describe a prognostic signature based on expression levels of CCL5, DDIT4 and POLR1C. The knowledge about the involvement of these genes in chemotherapy resistance could improve the therapeutic strategies in triple-negative breast cancer. [Sci Rep] Full Article

X-Linked Inhibitor of Apoptosis Protein Mediates Tumor Cell Resistance to Antibody-Dependent Cellular Cytotoxicity
Researchers demonstrated that the caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in inflammatory breast cancer (IBC), drives resistance to antibody-dependent cellular cytotoxicity (ADCC) mediated by cetuximab and trastuzumab. Overexpression of XIAP in parental IBC cell lines enhanced resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells rendered them sensitive. [Cell Death Dis] Full Article

CLINICAL RESEARCH

Afatinib plus Vinorelbine versus Trastuzumab plus Vinorelbine in Patients with HER2-Overexpressing Metastatic Breast Cancer Who Had Progressed on One Previous Trastuzumab Treatment (LUX-Breast 1): An Open-Label, Randomized, Phase III Trial
Scientists enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned to receive oral afatinib plus intravenous vinorelbine or intravenous trastuzumab plus vinorelbine. [Lancet Oncol] Abstract

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URMC Partners with Private Company to Create Tissue Bank for Cancer Research
The University of Rochester Medical Center (URMC) announced it’s collaborating with Indivumed, to establish a bank of human tissues and tumor samples that are expertly preserved and stored for use in cancer research. [University of Rochester Medical Center] Press Release

S&T Technique to Detect Breast Cancer Moving from Lab to Commercialization
Cancer screening could soon be as simple as giving a urine sample using a patented device developed by a Missouri University of Science and Technology (S&T) researcher. Wyoming-based Cancer.im Inc., announced an agreement with Missouri S&T to commercialize the device. [Missouri University of Science and Technology] Press Release

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NEW Manager – Medical and Breast Imaging (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Fellowship – Breast Cancer Biology (Washington University School of Medicine)

NEW Postdoctoral Fellowship – Breast Cancer Biology (University of Houston College of Pharmacy)

Professorship – Clinical Breast Cancer Research (University of Leeds)

Clinical Pathways Associate – Cancer Therapeutics (Fred Hutchinson Cancer Research Center)

Clinical Researcher – Breast Cancer (Massachusetts General Hospital-Cancer Center)

Postdoctoral Fellowship – Breast Cancer Development (University of Pennsylvania)

Academic Surgical Pathologist – Breast Pathology (Northwestern University)

Postdoctoral Fellowship – Breast Cancer Translational Research (University of Bern)

Postdoctoral Fellowship – Breast/Ovarian Cancer Therapeutics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellowship – Epidemiologist (German Cancer Research Center)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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