Mammary Cell News Volume 9.01 | Jan 12 2017

TOP STORY

New Insights into Mechanisms of Breast Cancer Development and Resistance to Therapy

Why does breast cancer develop and how come certain patients are resistant to established therapies? Researchers from the University of Basel have gained new insights into the molecular processes in breast tissue. They identified the tumor suppressor LATS as a key player in the development and treatment of breast cancer. [Press release from the University of Basel discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, plus PARP-Inhibitors in BRCA1/2-Wild-Type Triple-Negative Breast Cancer

The authors sought to investigate the combined DNA-damaging effects of the topoisomerase I-inhibitory activity of sacituzumab govitecan (IMMU-132) with poly(ADP-ribose) polymerase inhibitors (PARPi) disruption of DNA repair in triple-negative breast cancer (TNBC). Combining IMMU-132 in TNBC with all three different PARPi resulted in synergistic growth inhibition, increased double-stranded DNA breaks, and accumulation of cells in the S-phase of the cell cycle, regardless of BRCA1/2 status. [Clin Cancer Res] Abstract | Press Release

TRIM28 Interacts with EZH2 and SWI/SNF to Activate Genes that Promote Mammosphere Formation

Transcriptome profiling showed that Enhancer of Zeste Homolog 2 (EZH2) primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients. [Oncogene] Abstract

FBXO32 Suppresses Breast Cancer Tumorigenesis through Targeting KLF4 to Proteasomal Degradation

Krüppel-like factor 4 (KLF4) is critical for cell fate decision and has an ambivalent role in tumorigenesis. To better understand the mechanism of KLF4 ubiquitination, investigators performed a genome-wide screen of E3 ligase small interfering RNA library based on western blot and identified SCF-FBXO32 as a new E3 ligase, which is responsible for KLF4 ubiquitination and degradation. [Oncogene] Abstract

Bone Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth

Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In vitro, bisphosphonic based MMP-2 inhibitors (BMMPIs) impacted the viability of breast cancer cell lines and osteoclast precursors but not osteoblasts. In vivo, researchers demonstrated using two bone metastatic models that BMMPI treatment significantly reduced tumor growth and tumor associated bone destruction. [Mol Cancer Ther] Abstract

MicroRNA-494 Inhibits Breast Cancer Progression by Directly Targeting PAK1

Investigators showed that microRNA (miR)-494 is decreased in human breast cancer specimens and breast cancer cell lines. The expression of PAK1 was inversely correlated with the level of miR-494 in human breast cancer samples. [Cell Death Dis] Full Article

Cyclooxygenase-2 Regulates TGFβ-Induced Cancer Stemness in Triple-Negative Breast Cancer

The authors investigated the role of the cyclooxygenase-2 (COX-2), a downstream target of TGFβ, in regulating breast cancer stem cells in triple negative breast cancer (TNBC). Bioinformatics analysis revealed that COX-2 is highly expressed in TNBC and that its expression correlated with poor survival outcome in basal subtype of breast cancer. [Sci Rep] Full Article

IGF-IR Cooperates with ERα to Inhibit Breast Cancer Cell Aggressiveness by Regulating the Expression and Localization of ECM Molecules

Scientists report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix (ECM) molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. [Sci Rep] Full Article

BRCA1-IRIS Overexpression Promotes and Maintains the Tumor Initiating Phenotype: Implications for Triple Negative Breast Cancer Early Lesions

Researchers demonstrated that BRCA1-IRIS overexpression promotes triple negative breast cancers through suppressing BRCA1 expression, enhancing basal-biomarkers, epithelial-to-mesenchymal transition-inducers, and stemness-enforcers expression. [Oncotarget] Full Article

Secretion Modification Region-Derived Peptide Blocks Exosome Release and Mediates Cell Cycle Arrest in Breast Cancer Cells

The authors determined the effects of a peptide as an inhibitor of exosome secretion on breast tumors. PEG-Secretion Modification Region-wt-Clusterin peptides inhibited the growth of human breast cancer cells and blocked tumor exosome release in vitro. The peptide alone did not cause increased cytotoxicity or apoptosis induction, but did cause cell cycle G2/M phase arrest in both estrogen responsive and non-responsive breast cancer cells. [Oncotarget] Full Article

Short-Term Early Exposure to Lapatinib Confers Lifelong Protection from Mammary Tumor Development in MMTV-erbB-2 Transgenic Mice

In the syngeneic tumor transplant model, researchers determined that lapatinib significantly inhibited tumor cell proliferation. Furthermore, they demonstrated that short-term lapatinib exposure resulted in life-long protective effects, as supported by increased tumor latency in lapatinib-treated mice compared to the control mice. [J Exp Clin Cancer Res] Full Article

Discovery of Centrosomal Protein 70 as an Important Player in the Development and Progression of Breast Cancer

Scientists identified centrosomal protein 70 (Cep70) as an important factor that mediates breast cancer growth and metastasis. Cep70 was up-regulated in breast cancer tissues and cell lines, and its expression was closely correlated with several clinicopathologic variables associated with breast cancer progression. [Am J Pathol] Abstract

Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

The authors offer an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer. [Int J Mol Sci] Full Article

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

U.S. FDA Accepts Biologics License Application (BLA) for Mylan and Biocon’s Proposed Biosimilar Trastuzumab

Mylan N.V. and Biocon Ltd. announced that the U.S. Food and Drug Administration (FDA) has accepted Mylan’s biologics license application for MYL-1401O for filing through the 351(k) pathway. This product is a proposed biosimilar to branded trastuzumab, which is indicated to treat certain HER2-positive breast cancers. [Mylan N.V.] Press Release

Bristol-Myers Squibb Announces Immunotherapy Clinical Collaboration with Janssen to Evaluate Opdivo (Nivolumab) in Combination with Darzalex (Daratumumab)

Bristol-Myers Squibb Company announced a new clinical research collaboration with Janssen Biotech, Inc. to evaluate the combination of Bristol-Myers Squibb’s Immuno-Oncology agent Opdivo and Janssen’s CD38-directed cytolytic antibody Darzalex in Phase Ib/II clinical studies in multiple myeloma and solid tumors including non-small cell lung cancer, pancreatic cancer, colorectal cancer, triple negative breast cancer and head and neck cancer. [Bristol-Myers Squibb Company] Press Release

White House Announces Review Process for Risky Virus Studies

Federal officials released a plan to help U.S. agencies decide whether to fund controversial studies that make viruses more dangerous. The guidance may finally bring an end to a moratorium that has kept a handful of experiments funded by the Department of Health and Human Services on hold for more than two years. [ScienceInsider] Editorial

US Energy Agency Strengthens Protections for Scientists

The US Department of Energy has released new guidelines to protect researchers from political interference — a move that many say is long overdue. [Nature News] Editorial

NEW EFGCP Annual Conference 2017 on Meeting the Ethical Standards under the Clinical Trials Regulation
February 21-22, 2017
Brussels, Belgium

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

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

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

NEW 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)

Two Postdoctoral Opportunities – Cancer Epigenetics (International Agency for Research on Cancer)

Postdoctoral Fellow – Breast Cancer Biology (Icahn School of Medicine at Mount Sinai)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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