Mammary Cell News Volume 8.46 | Nov 24 2016

TOP STORY

Systemic Depletion of L-Cyst(e)ine with Cyst(e)inase Increases Reactive Oxygen Species and Suppresses Tumor Growth

Scientists showed that administration of an engineered and pharmacologically optimized human cyst(e)inase enzyme mediates sustained depletion of the extracellular L-cysteine (L-Cys) and L-Cys that is predominantly in its disulfide form pool in mice and non-human primates. Cyst(e)inase suppressed the growth of prostate carcinoma allografts, reduced tumor growth in both prostate and breast cancer xenografts and doubled the median survival time of TCL1-Tg:p53^−/− mice, which develop disease resembling human chronic lymphocytic leukemia. [Nat Med] Abstract | Press Release

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Full Antagonism of the Estrogen Receptor Without a Prototypical Ligand Side Chain

Resistance to endocrine therapies remains a major clinical problem for the treatment of estrogen receptor-α (ERα)-positive breast cancer. On-target side effects limit therapeutic compliance and use for chemoprevention, highlighting an unmet need for new therapies. Investigators present a full-antagonist ligand series lacking the prototypical ligand side chain that has been universally used to engender antagonism of ERα through poorly understood structural mechanisms. [Nat Chem Biol] Abstract | Press Release

IRS4 Induces Mammary Tumorigenesis and Confers Resistance to HER2-Targeted Therapy through Constitutive PI3K/AKT-Pathway Hyperactivation

Scientists showed that Irs4 expression in mammary epithelial cells induces constitutive PI3K/AKT pathway hyperactivation, insulin/IGF1-independent cell proliferation, anchorage-independent growth and in vivo tumorigenesis. [Nat Commun] Full Article

CELF1 Is a Central Node in Post-Transcriptional Regulatory Programs Underlying EMT

Investigators leverage polyribosomal profiling to prospectively define translational regulatory programs underlying epithelial-to-mesenchymal transition (EMT) in breast epithelial cells. They identified a group of ten translationally regulated drivers of EMT sharing a common GU-rich cis-element within the 3′-untranslated region of their mRNA. [Nat Commun] Full Article

Fibrous Nonlinear Elasticity Enables Positive Mechanical Feedback between Cells and ECMs

Mechanical interactions between cells and the three dimensional (3D) ECM critically regulate cell function, including growth and migration. However, the physical mechanism that governs the cell interaction with fibrous 3D ECM is still not known. Scientists present single-cell traction force measurements using breast tumor cells embedded within 3D collagen matrices. [Proc Natl Acad Sci USA] Abstract | Press Release

Breast Cancer Resistance to Antiestrogens Is Enhanced by Increased ER Degradation and ERBB2 Expression

In breast cancer cells rendered resistant to the antiestrogen fulvestrant, investigators defined causative mechanistic roles for the transcription factor YBX1 and the levels of estrogen receptor (ER) and the ERBB2 receptor. Enforced expression of YBX1 in parental cells conferred resistance against tamoxifen and fulvestrant in vitro and in vivo. [Cancer Res] Abstract

Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer

In order to fast-track clinical testing of potentially promising combinations, scientists systematically assessed the impact of 128 single agents in combinations with each of six drugs already approved by the US-FDA, resulting in 768 pairwise drug combinations covering a wide range of targets and processes implicated in cancer biology. They reported anticancer activity of drug combinations based on overall growth inhibition and synergistic drug effects in six triple-negative breast cancer cell lines. [Cancer Res] Abstract

Cystine Addiction of Triple-Negative Breast Cancer Associated with EMT Augmented Death Signaling

Researchers performed a nutrigenetic screen on a panel of breast cancer cells by removing single nutrient components and determining the resultant cellular and gene expression phenotypes. [Oncogene] Abstract | Press Release

TAp63 Suppresses Mammary Tumorigenesis through Regulation of the Hippo Pathway

The authors showed that the tumor suppressor and transcription factor, TAp63, regulates cell polarity and mammary stem cells through transcriptional regulation of LKB1 and downstream regulation of Scrib and components of the Hippo pathway. [Oncogene] Full Article

CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer

The authors report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of homologous recombination (HR). In BRCA-mutated triple-negative breast cancer cells and patient-derived xenografts, dinaciclib ablates restored HR and reverses poly(ADP-ribose) polymerase (PARP) inhibitor resistance. [Cell Rep] Full Article | Graphical Abstract

Vasohibin 2 Promotes Epithelial-Mesenchymal Transition in Human Breast Cancer via Activation of Transforming Growth Factor β1 and Hypoxia Dependent Repression of GATA-Binding Factor 3

To investigate the epithelial-mesenchymal transition role of vasohibin 2 (VASH2) in breast cancer, the authors overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. [Cancer Lett] Abstract

miR-96 Promotes Cell Proliferation, Migration and Invasion by Targeting PTPN9 in Breast Cancer

microRNAs have emerged as major regulators of the initiation and progression of human cancers, including breast cancer. Investigators determined the expression pattern of miR-96 in breast cancer and investigated its biological role during tumorigenesis. [Sci Rep] Full Article

Molecular Mechanisms of Asymmetric Divisions in Mammary Stem Cells

The authors provide a critical evaluation of the assays used to establish the stem cell mode of division, with a particular focus on the mammary gland system. [EMBO Rep] Abstract

Identifying Progression Predictors of Breast Ductal Carcinoma In Situ

Scientist review the roles of the tumor stroma (including mesenchymal cells, immune cells and the extracellular matrix) and myoepithelial cells in malignant progression and make a case for a more integrated approach to the study and assessment of ductal carcinoma in situ and its progression, or lack thereof, to invasive disease. [J Clin Pathol] Abstract

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

Celyad Announces the Approval to Initiate Its NKR-2 CAR-T Clinical Trial in Belgium

Celyad announced the approval in Belgium to initiate the THINK clinical trial. THINK is the second clinical trial of its NKR-2 product candidate, a CAR-T cell therapy using NKG2D ligands as a target, to evaluate safety and efficacy in seven refractory cancers including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma). [Celyad] Press Release

Ruga Corporation Announces Move to Houston with $20 Million Grant from CPRIT and Name Change to Aravive Biologics

Ruga Corporation announced the company’s name change to Aravive Biologics, Inc., and the relocation of its business operations to Houston, Texas. The move follows the company’s award of a $20 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT), which is supporting the development of a novel drug candidate, Aravive-S6, as a potential treatment for acute myelogenous leukemia and solid tumors including ovarian, pancreatic, and breast cancers. [Aravive Biologics, Inc.] Press Release

$25 Million Awarded to Center for Study of Regulatory Science

The FDA is funding a collaboration between Stanford and UCSF to improve the regulatory infrastructure that helps to shape modern biomedical research. [Stanford Medicine] Press Release

Salk Institute Awarded $25 Million Grant from Helmsley Charitable Trust

The Salk Institute for Biological Studies has received a $25 million grant—a renewal of the largest research gift in the Institute’s 56-year history—that will be used to continue exploring an ambitious range of projects aimed at understanding the role chronic inflammation plays in driving human disease. [Salk Institute for Biological Studies] Press Release

Center for Regenerative Medicine Receives Three Prestigious NIH Awards To Further Stem Cell Research

The Center for Regenerative Medicine at Boston Medical Center and Boston University School of Medicine has received three prestigious awards from the National Institutes of Health (NIH) to further its commitment to induced pluripotent stem cell research and education. [Boston University School of Medicine] Press Release

UK Scientists Excited by Surprise £2-Billion Government Windfall

UK Chancellor of the Exchequer Philip Hammond has announced a large boost in funding for research and development (R&D). The government is expecting to spend an extra £4.7 billion on R&D between now and 2020–21, and the final year’s £2-billion boost will represent a rise of around 20% in total government R&D spending. [Nature News] Editorial

NgAgo Gene-Editing Controversy Escalates in Peer-Reviewed Papers

A heated dispute over gene-editing that began online is now playing out in the scientific literature. Six months ago, Chinese researchers reported that an enzyme called NgAgo could be used to edit mammalian genes – and that it might be more accurate and more versatile than the popular CRISPR-Cas9 gene-editing technique. [Nature News] Editorial

Immigrant and Minority Scientists Shaken by Trump Win

Scientist are reconsidering whether to work or study in the United States. Worries include job prospects, discrimination — and safety. [Nature News] Editorial

Peer-Review ‘Heroes’ Do Lion’s Share of the Work

In 2015, the number of scientists in the life sciences far exceeded the demand on them for peer review, according to Michail Kovanis, a computational physicist at the French National Institute of Health and Medical Research in Paris, and his colleagues. Yet their study also suggests – based on data obtained from a rapidly-growing website of peer-review activity – that 20% of the scientists undertook between 69% and 94% of reviews last year, lending credence to some researchers’ complaints that they are overburdened. [Nature News] Editorial

NEW Interventional Orthopedics Foundation 2017 Annual Conference
February 17-18, 2017
Broomfield, United States

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

NEW Research Assistant – Bioinformatics (Cancer Research UK Cambridge Institute)

NEW Assistant Professor – Cancer Research (National University of Singapore)

NEW Postdoctoral Research Assistant – Cancer Research (Yale University)

NEW Postdoctoral Fellow – Immunotheraphy for Breast Cancer (Dalhousie Universtiy)

Research Fellow – Breast Cancer Research (Dana-Farber Cancer Institute)

Bioinformatician – Breast Cancer (Queen Mary University of London)

Postdoctoral Fellow – Cancer Prevention Studies (American Cancer Society)

Postdoctoral Position – Immunology (Inserm)

Postdoctoral Fellow – BioMarker Research Cancer (Houston Methodist Research Institute)

Postdoctoral Associate – Functional Genomics and Cancer (The Jackson Laboratory)

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