Mammary Cell News Volume 9.13 | Apr 6 2017

TOP STORY

Biomarker Identified for Likely Aggressive, Early Stage Breast Cancer

Researchers have identified SMARCE1, a gene overexpressed in the subset of early-stage cancers that are likely to become aggressively invasive – making it possible for the first time to distinguish poorly invasive tumors from those that will likely spread and metastasize. With such a biomarker, doctors could better tailor therapies designed to match the behavior of each patient’s cancer. [Press release from the Whitehead Institute for Biomedical Research discussing online prepublication in Nature Communications] Press Release | Full Article

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

USP9X Regulates Centrosome Duplication and Promotes Breast Carcinogenesis

Investigators report that the X-linked deubiquitinase USP9X was physically associated with centriolar satellite protein CEP131, thereby stabilizing CEP131 through its deubiquitinase activity. They demonstrated that USP9X is an integral component of centrosome and is required for centrosome biogenesis. USP9X was overexpressed in breast carcinomas, and its level of expression was correlated with that of CEP131 and higher histologic grades of breast cancer. [Nat Commun] Full Article

Fibroblasts Drive an Immunosuppressive and Growth-Promoting Microenvironment in Breast Cancer via Secretion of Chitinase 3-Like 1

Researchers report a novel signaling axis between fibroblasts, cancer cells and immune cells in breast tumors that drives an immunosuppressive microenvironment, mediated by cancer-associated fibroblast (CAF)-derived Chi3L1. They demonstrated that Chi3L1 is highly upregulated in CAFs isolated from mammary tumors and pulmonary metastases of transgenic mice, and in the stroma of human breast carcinomas. [Oncogene] Full Article

Neuromedin U Alters Bioenergetics and Expands the Cancer Stem Cell Phenotype in HER2-Positive Breast Cancer

The authors found that ectopic over-expression of neuromedin U (NmU) in HER2-positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity. Overexpression of NmU also resulted in upregulation of epithelial-mesenchymal transition markers and increased IL-6 secretion which, together with aberrant metabolism, have all been associated with the cancer stem cell phenotype. [Int J Cancer] Abstract

cPLA2α Mediates TGF-β-Induced Epithelial-Mesenchymal Transition in Breast Cancer through PI3k/Akt Signaling

Scientists found that cPLA2α was commonly overexpressed in most human breast cancer tissues and significantly correlated with a poor prognosis for human breast cancer. Functional studies demonstrated that cPLA2α overexpression was significantly associated with elevated migration and invasion in MDA-MB-231 and T47D cells. [Cell Death Dis] Full Article

ZEB1 Induces ER-α Promoter Hypermethylation and Confers Antiestrogen Resistance in Breast Cancer

Researchers report that ectopic zinc-finger E-box binding homeobox 1 (ZEB1) was associated with ER-α deficiency in breast cancer cells and thus conferred antiestrogen resistance. Mechanistically, ZEB1 repressed ER-α transcription by forming a ZEB1/DNA methyltransferase 3B/histone deacetylase 1 complex on the ER-α promoter, leading to DNA hypermethylation and the silencing of ER-α. [Cell Death Dis] Full Article

Lipin-1 Regulation of Phospholipid Synthesis Maintains Endoplasmic Reticulum Homeostasis and Is Critical for Triple-Negative Breast Cancer Cell Survival

Investigators found that LPIN1, which encodes lipin-1, a phosphatidic acid phosphatase controlling the rate-limiting step in the phospholipid synthesis pathway, is highly up-regulated in basal-like triple-negative breast cancer. High LPIN1 expression correlated with the poor prognosis of these patients. [FASEB J] Abstract

Loss of p27^kip1 Increases Genomic Instability and Induces Radio-Resistance in Luminal Breast Cancer Cells

Cyclin-dependent kinases (CDKs) take part in safeguarding mechanisms, but involvement of CDK-inhibitors, such as p27^kip1, is less clear. Scientists generated immortalized fibroblasts from p27^kip1 knock-out mouse embryos and re-expressed p27^kip1 wild type, or its mutant forms, to identify the function of different domains. [Sci Rep] Full Article

Preparation and Characterization of (−)-Epigallocatechin-3-Gallate (EGCG)-Loaded Nanoparticles and Their Inhibitory Effects on Human Breast Cancer MCF-7 Cells

Investigators employed nanotechnology to improve the targeting ability of EGCG towards MCF-7 cells, and two kinds of EGCG nanoparticles were obtained. Their characteristics and effects on MCF-7 cells were studied. [Sci Rep] Full Article

Patterns of Cell Cycle Checkpoint Deregulation Associated with Intrinsic Molecular Subtypes of Human Breast Cancer Cells

Scientists assessed the Gap 2 and mitotic checkpoint functions of 24 breast cancer and immortalized mammary epithelial cell lines representing four of the six intrinsic molecular subtypes of breast cancer. They found that patterns of cell cycle checkpoint deregulation were associated with the intrinsic molecular subtype of breast cancer cell lines. [NPJ Breast Cancer] Full Article

CLINICAL RESEARCH

Efficacy of the PARP Inhibitor Veliparib with Carboplatin or as a Single Agent in Patients with Germline BRCA1- or BRCA2-Associated Metastatic Breast Cancer

Investigators aimed to establish the maximum tolerated dose of the poly(ADP-ribose) (PAR) polymerase inhibitor, veliparib, in combination with carboplatin in germline BRCA1- and BRCA2-associated metastatic breast cancer, to assess the efficacy of single-agent veliparib, and of the combination treatment post-progression, and to correlate PAR levels with clinical outcome. [Clin Cancer Res] Abstract

Wnt Signaling in Triple-Negative Breast Cancer

The authors summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of triple-negative breast cancer (TNBC). They review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease. [Oncogenesis] Full Article

The Opportunity of Precision Medicine for Breast Cancer with Context-Sensitive Tumor Suppressor Maspin

Scientists discuss the possibility for maspin to serve as a cell type-specific and context-sensitive marker to improve the precision of breast cancer diagnosis and prognosis. These advancements further suggest a new window of opportunity for designing novel maspin-based chemotherapeutic agents with improved anti-cancer potency. [J Cell Biochem] Abstract

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Puma Biotechnology Presents Interim Results of Phase II CONTROL Trial of PB272 in Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer

Puma Biotechnology, Inc. announced that interim results from a Phase II clinical trial of Puma’s investigational drug PB272 were presented. [Press release from Puma Biotechnology, Inc. discussing research presented at the 2017 American Association for Cancer Research Annual Meeting (AACR), Washington, D.C.] Press Release

Puma Biotechnology Presents Interim Results of Phase Ib/II FB-10 Trial of PB272 in Combination with Trastuzumab Emtansine (T-DM1) in HER2-Positive Metastatic Breast Cancer

Puma Biotechnology, Inc. announced that interim results from the Phase Ib/II FB-10 clinical trial of Puma’s investigational drug PB272 given in combination with the antibody drug conjugate T-DM1 were presented. [Press release from Puma Biotechnology, Inc. discussing research presented at the 2017 American Association for Cancer Research Annual Meeting (AACR), Washington, D.C.] Press Release

Oncolytics Biotech^® Inc.’s REOLYSIN^® More Than Doubles Overall Survival in Patients with Mutated p53 Metastatic Breast Cancer

Oncolytics Biotech^® Inc. announced data demonstrating a statistically significant overall survival benefit for patients with mutated p53 metastatic breast cancer, when treated with REOLYSIN^®, an immuno-oncology viral agent, in combination with paclitaxel. Results from IND 213, an open-label, randomized, Phase II study were presented. [Press release from Oncolytics Biotech^® Inc. discussing research presented at the 2017 American Association for Cancer Research Annual Meeting (AACR), Washington, D.C.] Press Release

Mena Expression Is Associated with Paclitaxel-Mediated Increase in Cancer Cell Dissemination

MetaStat, Inc. announced the presentation of supportive data for the role of Mena protein isoforms in tumor dissemination. In the current study of tumor-bearing mice, paclitaxel treatment was shown to increase the number of MetaSites, circulating tumor cells and lung metastasis. [Press release from MetaStat, Inc. discussing research presented at the 2017 American Association for Cancer Research Annual Meeting (AACR), Washington, D.C.] Press Release

IBRANCE^® (Palbociclib) Receives FDA Regular Approval and Expanded Indication for First-Line HR⁺, HER2^– Metastatic Breast Cancer

Pfizer Inc. announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application for its first-in-class cyclin dependent kinase 4/6 inhibitor, IBRANCE^®, based on the results from the confirmatory Phase III trial PALOMA-2. [Pfizer Inc.] Press Release

Susan G. Komen^® Names Eight Advisors to Guide Renowned Breast Cancer Research Program

Susan G. Komen announced new advisory roles for eight leaders in breast cancer who will guide the organization’s education and advocacy work, public health efforts and help direct Komen’s $920 million research program – an investment in breast cancer research surpassed only by the U.S. government. [Susan G. Komen (Business Wire, Inc.)] Press Release

Japanese Scientists Call for Boycott of Military Research

The Science Council of Japan, an advisory body to the cabinet, representing some 850,000 Japanese scientists, released a statement calling on scientists to boycott military research and for universities and research organizations to evaluate the threats posed by such work. [Nature News] Editorial

Initiative Aims to Break Science’s Citation Paywall

The Initiative for Open Citations (I4OC) aims to allow anyone to access science papers’ reference lists and to build analytical services on top of that raw data. Started by the Wikimedia Foundation in San Francisco, California and five other partner organizations, I4OC announced at its official launch that 29 organizations, including some of the world’s largest scientific publishers, have now agreed to openly release citation data. [Nature News] Editorial

NEW Rapid Signaling and Genomic Steroid Hormone Actions in Health and Disease
June 11-16, 2017
Snowmass Village, United States

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NEW Postdoctoral Research – Cancer Biology (University of Pennsylvania)

NEW Research Fellow – Molecular Biology (Monash University)

Bioinformatics Scientist – Breast Cancer (Windber Research Institute)

Postdoctoral Fellow – Genetics, Genomics and Informatics (The University of Tennessee Health Science Center)

Postdoctoral Fellow – Breast Cancer Stem Cell (University of Kentucky)

Postdoctoral Position – Metastatic Breast Cancer (Purdue University)

Research Assistant/Associate – Breast Cancer Biology (Icahn School of Medicine at Mount Sinai)

Assistant or Associate Professor – Breast Cancer Research (Georgetown University School of Medicine)

Postdoctoral Position – Breast Cancer (Memorial Sloan Kettering Cancer Center)

Postdoctoral Research Scholar – Breast Tumor Growth (University of Iowa)

Postdoctoral Fellow – Proteoglycans (Thomas Jefferson University)

Postdoctoral Fellow – Cancer Research (Houston Methodist Research Institute)

Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine)

Assistant or Associate Professor – Breast Cancer (Roswell Park Cancer Institute)

Postdoctoral Associate – Mammary Stem Cell and Cancer Biology (University of Miami)

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