Mammary Cell News Volume 10.34 | Aug 30 2018

TOP STORY

Epigenetic and Transcriptomic Profiling of Mammary Gland Development and Tumor Models Disclose Regulators of Cell State Plasticity

Researchers found that DNA-binding motifs for SOX transcription factors were enriched in chromatin that is accessible in stem/progenitor cells and inaccessible in differentiated cells. In both mouse and human tumors, SOX10 expression correlated with stem/progenitor identity, dedifferentiation, and invasive characteristics. [Cancer Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

IL-1β Inflammatory Response Driven by Primary Breast Cancer Prevents Metastasis-Initiating Cell Colonization

At the metastatic site, interleukin-1β (IL-1β) maintained metastasis-initiating cancer cells (MICs) in a ZEB1-positive differentiation state, preventing MICs from generating highly proliferative E-cadherin-positive progeny. Ablation of the pro-inflammatory response or inhibition of the IL-1 receptor relieved the differentiation block and resulted in metastatic colonization. [Nat Cell Biol] Abstract | Press Release

Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway

Inhibition of the phosphocreatine energy shuttle by mitochondrial creatine kinase 1 knockdown or with the creatine analog cyclocreatine decreased proliferation of trastuzumab-sensitive and -resistant HER2⁺ cell lines in culture and in xenografts. [Cell Metab] Abstract | Press Release | Graphical Abstract

Target Identification of Yaku’amide B and Its Two Distinct Activities against Mitochondrial FoF1-ATP Synthase

Investigators showed that yaku’amide B (1b) selectively accumulated in the mitochondria of MCF-7 human breast cancer cells. They showed that 1b inhibited ATP production catalyzed by mitochondrial FoF1-ATP synthase. Remarkably, 1b was also found capable of enhancing the ATP hydrolytic activity of FoF1-ATP synthase. [J Am Chem Soc] Abstract

Polycomb Complexes Associate with Enhancers and Promote Oncogenic Transcriptional Programs in Cancer through Multiple Mechanisms

Scientists found that canonical polycomb repressive complex 1 complexes functionally associated with estrogen receptor alpha and its pioneer factor FOXA1 in ER+ breast cancer cells, and with BRD4 in triple-negative breast cancer cells. RING1B regulated enhancer activity and gene transcription not only by promoting the expression of oncogenes but also by regulating chromatin accessibility. [Nat Commun] Full Article

In Vivo Phosphoproteomics Reveals Kinase Activity Profiles that Predict Treatment Outcome in Triple-Negative Breast Cancer

The authors used high-throughput phosphoproteomics to build a functional triple-negative breast cancer (TNBC) taxonomy. Drug regimens designed based on six kinases showed promising antitumor activity in TNBC cell lines and patient-derived xenografts. [Nat Commun] Full Article | Press Release

The Pleiotropic Effects of TNFα in Breast Cancer Subtypes Is Regulated by TNFAIP3/A20

TNFα induced potent cytotoxic cell death in luminal breast cancer cell lines which failed to upregulate TNFAIP3 (A20) expression. Overexpression of A20 not only protected luminal breast cancer cell lines from TNFα-induced cell death via inducing HSP70-mediated anti-apoptotic pathway but also promoted a robust EMT/CSC phenotype by activating pStat3-mediated inflammatory signaling. [Oncogene] Abstract

IITZ-01, a Novel Potent Lysosomotropic Autophagy Inhibitor, Has Single-Agent Antitumor Efficacy in Triple-Negative Breast Cancer In Vitro and In Vivo

Investigators discovered that both IITZ-01 and IITZ-02 act as potent autophagy inhibitors. Treatment with these compounds resulted in the vacuolated appearance of cells due to their specific accumulation in lysosomes. IITZ-01 and IITZ-02 enhanced autophagosome accumulation but inhibited autophagosomal degradation by impairing lysosomal function, finally resulting in the inhibition of autophagy. [Oncogene] Abstract

Synergistic Inhibition of Aggressive Breast Cancer Cell Migration and Invasion by Cytoplasmic Delivery of Anti-RhoC Silencing RNA and Presentation of EPPT1 Peptide on “Smart” Particles

The authors showed that “smart” nanoparticles successfully delivered anti-RhoC siRNA into the cytoplasm of aggressive SUM149 and MDA-MB-231 breast cancer cells, which resulted in a dose-dependent inhibition of cell migration and invasion. [J Control Release] Abstract | Graphical Abstract

Overexpression of CDCA7 Predicts Poor Prognosis and Induces EZH2-Mediated Progression of Triple-Negative Breast Cancer

Scientists observed that CDCA7 silencing in triple-negative breast cancer cell lines effectively impaired cell proliferation, invasion and migration in vitro. CDCA7 increased the expression of EZH2, a marker of aggressive breast cancer that is involved in tumor progression, by enhancing the transcriptional activity of its promoter. [Int J Cancer] Abstract

Evaluating Nanoshells and a Potent Biladiene Photosensitizer for Dual Photothermal and Photodynamic Therapy of Triple Negative Breast Cancer Cells

Researchers evaluated a dual photothermal therapy (PTT)/photodynamic therapy (PDT) strategy for treatment of triple negative breast cancer cells mediated by a powerful combination of silica core/gold shell nanoshells and palladium 10,10-dimethyl-5,15-bis(pentafluorophenyl)biladiene-based photosensitizers, which enabled PTT and PDT, respectively. [Nanomaterials (Basel)] Full Article

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The Viral Approach to Breast Cancer Immunotherapy

The authors discuss the latest advancements in the applications of oncolytic viruses and bacterial viruses display systems as new and advanced modalities in cancer immune therapeutics. [J Cell Physiol] Abstract

Role for Growth Regulation by Estrogen in Breast Cancer 1 (GREB1) in Hormone-Dependent Cancers

GREB1 is an early estrogen-responsive gene, and its expression is correlated with estrogen levels in breast cancer patients. Scientists examine evidence that GREB1 participates in several hormone-dependent cancers and could be targeted to treat these cancers. [Int J Mol Sci] Full Article

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

Jefferson and Monell Center Sign Agreement of Cooperation

The Monell Center and Jefferson (Philadelphia University + Thomas Jefferson University) announced the signing of an Agreement of Cooperation, outlining how the two institutions will collaborate over the next year to develop joint scientific programs and clinical opportunities to advance their shared mission of improving human health. [Thomas Jefferson University] Press Release

Researchers to Test Novel Drug Combination against Toughest Breast Cancers

Researchers at University of California San Diego School of Medicine have launched a Phase Ib clinical trial to assess the safety and tolerability of cirmtuzumab, in combination with standard chemotherapy, to treat metastatic or locally advanced breast cancer that cannot be surgically removed. [University of California San Diego] Press Release

Baylor Awarded CPRIT Grants for Research, Recruitment

Baylor College of Medicine has been awarded more than $31 million by the Cancer Prevention & Research Institute of Texas (CPRIT) to support new research, core facilities and recruitment of new faculty to support the fight against cancer. [Baylor College of Medicine] Press Release

Forbius (Formation Biologics) Awarded $18.8 Million Grant by the Cancer Prevention and Research Institute of Texas

This grant will support additional preclinical and translational research, manufacturing, personnel costs, and clinical development of AVID100 in patients with confirmed EGFR overexpression in three Phase IIa clinical trials: breast cancer, squamous cell carcinoma of the head and neck, and non-small cell lung cancer. [Forbius] Press Release

UCHealth Patients in Northern Colorado Step Forward to Speed Advances in Cancer Care

UCHealth Poudre Valley Hospital (UCHealth) is among the nation’s first community hospitals to collaborate with leading academic medical centers and researchers through personalized medicine consortium. The members collect and share patient data with the goal of better understanding cancer at the molecular level and more precisely assigning treatment to patients. [UCHealth] Press Release

Top UK Genomics Institute Investigates Bullying Allegations

An investigation into allegations of bullying is under way at one of the world’s top genomics centers — the Wellcome Sanger Institute in Hinxton, UK. According to The Guardian, which first reported on the investigation at Sanger, the complaints come from current and former staff members and include allegations against the institute’s director, geneticist Michael Stratton, who has been at the helm since 2010. [Nature News] Editorial

Yale Prof Gets Endowed Chair Four Years after Harassment Finding

Michael Simons, a Yale School of Medicine professor who was removed from a leadership post in 2014 after the university found him guilty of sexual harassment, was given an endowed professorship in the school’s cardiology department. In response, faculty members “went into an uproar,” and the school removed an online press release about Simons’s honor, Yale Daily News reported. [The Scientist] Editorial

New Research: Financial Disclosure Lacking in Publication of Clinical Trials

A substantial proportion of pharmaceutical industry payments to authors of oncology clinical trials published in major scientific journals are not disclosed, new research shows. The publications focused on clinical trials that tested new cancer drugs. The new findings were published as a research letter in the journal JAMA Oncology. [OHSU] Editorial

NEW International Society for Stem Cell Research (ISSCR) 2019 Annual Meeting
June 26-29, 2019
Los Angeles, California, United States

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

NEW Postdoctoral Position – Cancer Biology (GIGA – Universite de Liege)

NEW Research Assistant II – Breast Medical Oncology (MD Anderson Cancer Center)

Cancer Faculty Investigators – Breast Cancer (The University of Alabama)

Tenure-Track Assistant Professor – Breast Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Fellow/Research Scientist – Cancer Research (Icahn School of Medicine at Mount Sinai)

Postdoctoral Positions – Breast Cancer Research (UPMC Hillman Cancer Center)

Cancer Faculty Investigators – Cancer Research (University of Alabama at Birmingham)

Postdoctoral Research Fellow – Immuno/Oncology of Breast Cancer (Henry M. Jackson Foundation)

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

Postdoctoral Position – Breast Cancer (University of Trento)

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