Mammary Cell News Volume 9.02 | Jan 19 2017

TOP STORY

α3 Chains of Type V Collagen Regulate Breast Tumor Growth via Glypican-1

The authors showed that α3(V) chains are an abundant product of normal mammary gland basal cells, and that α3(V) ablation in a mouse mammary tumor model inhibits mammary tumor progression by reducing the proliferative potential of tumor cells. A mechanism was presented for microenvironmental influence on tumor growth. α3(V) chains, produced in both basal-like and luminal human breast tumors, and its expression levels are tightly coupled with those of glypican-1 across breast cancer types. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Stress Granule-Associated Protein G3BP2 Regulates Breast Tumor Initiation

Investigators describe a chemical screening strategy to identify small molecules that enhance the effect of chemotherapeutic agents on tumor-initiating cells-enriched breast cancer cells. They identified proteins that interact with the lead compound C108, including the stress granule-associated protein, GTPase-activating protein (SH3 domain)-binding protein 2, G3BP2. [Proc Natl Acad Sci USA] Abstract | Press Release

β-Catenin Haploinsufficiency Promotes Mammary Tumorigenesis in an ErbB2-Positive Basal Breast Cancer Model

Scientists show that part of the challenge in antagonizing β-catenin is caused by its dual functionality as a cell adhesion molecule and a signaling molecule. In a mouse model of basal ErbB2 receptor tyrosine kinase 2 (ErbB2)-positive breast cancer, which exhibits aberrant β-catenin nuclear signaling, β-catenin haploinsufficiency induced aggressive tumor formation and metastasis by promoting the disruption of adherens junctions, dedifferentiation, and an epithelial to mesenchymal transition transcriptional program. [Proc Natl Acad Sci USA] Abstract

MDM4 Is a Rational Target for Treating Breast Cancers with Mutant p53

Investigators report that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like breast cancer (BC) samples. They demonstrated that conditional knockdown of MDM4 provoked growth inhibition across a range of breast cancer subtypes with mutant p53, including, luminal, Her2⁺ and triple negative BCs. [J Pathol] Abstract

Monomethyltransferase SETD8 Regulates Breast Cancer Metabolism via Stabilizing Hypoxia-Inducible Factor 1α

Scientists report that SETD8 was a positive regulator of anabolic metabolism. SETD8 reprogrammed breast cancer cell metabolism through hypoxia-inducible factor 1α (HIF1α) mediated process. They demonstrated that SETD8 was a HIF1α transcription target. [Cancer Lett] Abstract

IL-1β Induces Up-Regulation of BIRC3, a Gene Involved in Chemoresistance to Doxorubicin in Breast Cancer Cells

Inflammatory cytokine 1β (IL-1β)-induced epithelial to mesenchymal transition triggers the expression of markers associated with malignancy. Researchers report the expression of cell survival genes after IL-1β stimulation of an IL-1β-highly responsive clone. Cells stimulated with IL-1β when challenged with doxorubicin showed resistance to the drug, whereas silencing of BIRC3 decreased viability of the cells treated with the drug. [Cancer Lett] Abstract

CRB3 Regulates Contact Inhibition by Activating the Hippo Pathway in Mammary Epithelial Cells

The authors showed that CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions. They report that CRB3 acts as an upstream regulator of the Hippo pathway to regulate contact inhibition by recruiting other Hippo molecules, such as Kibra and/or FRMD6, in mammary epithelial cells. [Cell Death Dis] Full Article

Sorafenib Analogue SC-60 Induces Apoptosis through the SHP-1/STAT3 Pathway and Enhances Docetaxel Cytotoxicity in Triple-Negative Breast Cancer Cells

Researchers tested a sorafenib analogue SC-60, which lacks angiokinase inhibition activity but acts as a Src homology region 2 domain-containing phosphatase-1 (SHP-1) agonist, in triple-negative breast cancer (TNBC) cells. SC-60 inhibited proliferation and induced apoptosis by dephosphorylating STAT3 in both a dose- and time-dependent manner in TNBC cells. [Mol Oncol] Abstract | Full Article

Benzyl Isothiocyanate Potentiates p53 Signaling and Antitumor Effects against Breast Cancer through Activation of p53-LKB1 and p73-LKB1 Axes

Using a phosphoprotein-screening array, scientists found that benzyl isothiocynate (BITC) increases p53 phosphorylation in breast cancer cells and reveals an important role of ERK and PRAS40/MDM2 in BITC-mediated p53 activation. They showed that BITC rescues and activates p53-signaling network and inhibits growth of p53-mutant cells. [Sci Rep] Full Article

In Vivo and In Vitro Effects of microRNA-27a on Proliferation, Migration and Invasion of Breast Cancer Cells through Targeting of SFRP1 Gene via Wnt/β-Catenin Signaling Pathway

This study aimed to explore the effects of microRNA-27a (miR-27a) targeting of SFRP1 on the proliferation, migration and invasion of breast cancer (BC) cells through the regulation of Wnt/β-catenin signaling pathway. BC tissues were found to have higher miR-27a expression and lower SFRP1 mRNA and protein expressions than MCF-10A cells and normal breast tissues. [Oncotarget] Full Article

Cleavage of Fibulin-2 by the Aggrecanases ADAMTS-4 and ADAMTS-5 Contributes to the Tumorigenic Potential of Breast Cancer Cells

The authors investigated the ability of the secreted metalloproteases ADAMTS-4 and ADAMTS-5 to digest Fibulin-2. Using in vitro approaches and cultured breast cancer cell lines they demonstrated that Fibulin-2 is a better substrate for ADAMTS-5 than it is for ADAMTS-4. [Oncotarget] Full Article

Resveratrol Limits Epithelial to Mesenchymal Transition through Modulation of KHSRP/hnRNPA1-Dependent Alternative Splicing in Mammary Gland Cells

Researchers showed that resveratrol counteracts the TGF-β-induced epithelial to mesenchymal transition phenotype in mammary gland cells and affects the alternative exon usage of pre-mRNAs that encode crucial factors in adhesion and migration – including CD44, ENAH, and FGFR2 – in a panel of immortalized and transformed mammary gland cells. [Biochim Biophys Acta] Abstract

Mammary Stem Cells: Angels or Demons in Mammary Gland?

The authors review current knowledge of mammary epithelial hierarchy, highlighting the roles of mammary stem/progenitor cells and breast cancer stem cells along with their key molecular regulators in organ development and cancer evolution. Clarifying these issues will pave the way for developing novel interventions toward stem/progenitor cells in either prevention or treatment of breast cancer. [Signal Transduct Target Ther] Full Article

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

Daiichi Sankyo Initiates Phase I/II Study of Novel Antibody Drug Conjugate U3-1402 in Patients with HER3-Positive Metastatic or Unresectable Breast Cancer

Daiichi Sankyo Company, Ltd. announced the initiation of a three-part open-label Phase I/II study in Japan with U3-1402, a novel HER3-targeting antibody drug conjugate, in patients with HER3-positive metastatic or unresectable breast cancer who are refractory or intolerant to standard treatment, or for whom no standard treatment is available. [Daiichi Sankyo Company, Ltd.] Press Release

Xcovery Joins National Cancer Institute (NCI) Formulary to Help Expedite Cancer Clinical Trials

Xcovery announced their participation in the National Cancer Institute (NCI) Formulary, a public-private partnership between the NCI, part of the National Institutes of Health, and pharmaceutical and biotechnology companies to expedite the use of agents in clinical trials. The partnership, which launched with fifteen targeted agents from six pharmaceutical companies, will seek to alleviate the lengthy process to develop new therapies for patients, and respond to the call for greater collaboration within the industry made by Vice President Biden’s Cancer Moonshot Initiative. [Xcovery] Press Release

Mystery as Controversial List of Predatory Publishers Disappears

A popular blog that lists “potential, possible, or probable predatory” publishers and journals has disappeared, but it is not clear why. A University of Colorado in Denver spokesperson told ScienceInsider that Beall made a “personal decision” to take down his list of low-quality journals that charge authors a fee to publish, often with little or no review or editing. [ScienceInsider] Editorial

Gene-Edited Animals Face US Regulatory Crackdown

Researchers transforming animals with the latest genome-engineering tools may be disappointed by draft rules released by the US Food and Drug Administration (FDA). The most controversial of three proposed regulations declares that all animals whose genomes have been intentionally altered will be examined for safety and efficacy in a process similar to that for new drugs. Many researchers had hoped that the FDA would be less stringent about evaluating organisms whose genomes have been edited with precise tools — such as CRISPR and a separate technique called TALENs — than it is for animals that have been given DNA from different species or created using less-sophisticated means. [Nature News] Editorial

Billion-Dollar Project Aims to Prep Vaccines before Epidemics Hit

SARS, Zika, Ebola – when some of the world’s most terrifying disease outbreaks occur, health workers often find themselves powerless. A billion-dollar initiative aims to change that situation by pre-emptively developing and stockpiling vaccines to combat potential epidemic threats. [Nature News] Editorial

NEW Keystone Symposium: Tumor Metabolism: Mechanisms and Targets
March 5-9, 2017
Whistler, Canada

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

NEW Postdoctoral Researcher – Breast Cancer (National University of Ireland, Galway)

NEW Research Scientist – Oncology Research (MedImmune)

Postdoctoral Associate – Department of Therapeutic Radiology (Yale University School of Medicine)

Postdoc Positions – Molecular Cancer Biology and Bioinformatics (University of Pittsburgh)

Postdoctoral Fellow – Computational Cancer Biology (European Molecular Biology Laboratory)

Postdoc Position – Mammary Epithelium and Breast Cancer (Helmholtz Association)

Postdoctoral Fellow – Breast Cancer (University of Hawaii Cancer Center)

Postdoctoral Fellow – Cancer Biology (University of Illinois)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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