Mammary Cell News Volume 7.38 | Oct 1 2015

BAP1 Promotes Breast Cancer Cell Proliferation and Metastasis by Deubiquitinating KLF5
Investigators showed that, in breast cancer cells, KLF5 is stabilized by the deubiquitinase (DUB) BAP1. With a genome-wide siRNA library screen of DUBs, they identified BAP1 as a bona fide KLF5 DUB. BAP1 interacts directly with KLF5 and stabilizes KLF5 via deubiquitination. [Nat Commun] Full Article

CPEB1 Mediates Epithelial-to-Mesenchyme Transition and Breast Cancer Metastasis
Researchers showed that cytoplasmic polyadenylation element binding protein 1 (CPEB1)-depleted mammary epithelial cells alter their gene expression profile in a manner consistent with an epithelial-to-mesenchyme transition (EMT) and also become motile, which are made particularly robust when cells are treated with transforming growth factor-β, an enhancer of EMT. [Oncogene] Abstract

LncRNA-Hh Strengthen Cancer Stem Cells Generation in Twist-Positive Breast Cancer via Activation of Hedgehog Signaling Pathway
Investigators discovered that a set of long non-coding RNAs (lncRNAs) were dysregulated in Twist-positive mammosphere cells using lncRNA microarray analysis. The activated hedgehog signaling (Hh) increased GLI1 expression, and enhanced the expression of SOX2 and OCT4 to play a regulatory role in cancer stem cell maintenance. [Stem Cells] Abstract

Mitochondrial Mass, a New Metabolic Biomarker for Stem-Like Cancer Cells: Understanding WNT/FGF-Driven Anabolic Signaling
Researchers developed an isogenic cell model of “stemness” to facilitate protein biomarker discovery in breast cancer. Many of the proteins that were up-regulated by WNT/FGF-signaling in MCF7 cells, were also transcriptionally over-expressed in human breast cancer cells in vivo, based on the bioinformatic analysis of public gene expression datasets of laser-captured patient samples. [Oncotarget] Full Article

Endoplasmic Reticulum Protein 29 (ERp29) Confers Radioresistance through the DNA Repair Gene, O⁶-Methylguanine DNA-Methyltransferase, in Breast Cancer Cells
The authors reported that ERp29 expression in the triple negative MDA-MB-231 breast cancer cells significantly increased cell survival against ionizing radiation. [Sci Rep] Full Article

DEC1 Regulates Breast Cancer Cell Proliferation by Stabilizing Cyclin E Protein and Delays the Progression of Cell Cycle S Phase
Using the breast cancer cell lines MCF-7 and T47D, scientists showed that DEC1 could inhibit the cell cycle progression of breast cancer cells independently of its transcriptional activity. [Cell Death Dis] Full Article

Antidiabetic Exendin-4 Activates Apoptotic Pathway and Inhibits Growth of Breast Cancer Cells
Exendin-4 is a GLP-1 analog used for the treatment of type 2 diabetes mellitus in its synthetic form. Investigators examined the effect of the incretin drug exendin-4 on breast cancer cells. [Tumor Biol] Abstract

Breast Cancer Cell Line Aggregate Morphology Does Not Predict Invasive Capacity
To further assess the capacity of cell and aggregate morphology to predict invasive capacity in physiologically relevant environments, six cell lines with varied cell aggregate morphologies were assessed in a variety of assays including a 3D multicellular invasion assay that recapitulates cell-cell and cell-environment contacts as they exist in vivo in the context of the primary breast tumor. [PLoS One] Full Article

Modulating Mammary Tumor Growth, Metastasis and Immunosuppression by siRNA-Induced MIF Reduction in Tumor Microenvironment
Researchers developed small interfering RNA (siRNA)-loaded nanoparticle system to effectively reduce migration inhibitory factor (MIF) expression in both breast cancer cells and macrophages. Using this nanoparticle system, they demonstrated that the siRNA-induced MIF reduction in murine mammary cancer line 4T1 and human breast cancer line MDA-MB-231 resulted in significant reduction of cell proliferation and increase of apoptosis. [Cancer Gene Ther] Abstract

CLINICAL RESEARCH

A Phase I Study of a Heterologous Prime-Boost Vaccination Involving a Truncated HER2 Sequence in Patients with HER2-Expressing Breast Cancer
A Phase I clinical trial was conducted to assess the safety, tolerability, and preliminary efficacy of a heterologous prime-boost strategy involving plasmid DNA and an adenoviral vector, in patients with stage III–IV metastatic breast cancer expressing human epidermal growth factor receptor 2 (HER2). [Sci Rep] Full Article

Impact of Prior Anthracycline or Taxane Use on Eribulin Effectiveness as First-Line Treatment for Metastatic Breast Cancer: Results from Two Phase II, Multicenter, Single-Arm Studies
Phase II trials showed clinical activity and acceptable tolerability of first-line eribulin and eribulin plus trastuzumab. [Springerplus] Full Article

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First Human Patient Treated in Phase Ib Study of Advaxis’s ADXS-HER2 in HER2 Expressing Solid Tumors
Advaxis, Inc. announced that the first patient was treated in a Phase Ib dose-escalation clinical study of ADXS-HER2 for the treatment of patients with metastatic HER2 expressing solid tumors. [Advaxis, Inc.] Press Release

Stand Up To Cancer Canada – Canadian Breast Cancer Foundation Dream Team Is Announced
A Stand Up To Cancer Canada Dream Team researching new approaches to treating triple-negative breast cancer and other aggressive types of breast cancer has been formed thanks to a $9 million investment from a coalition of funders. [Canadian Breast Cancer Foundation] Press Release

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NEW Postdoctoral Fellow – Tumor Dormancy (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Scientist – Breast Cancer (Cancer Research UK Beatson Institute)

Postdoctoral Fellow – Breast Cancer Research (University Health Network)

Research Scientist – Epithelial Stem Cells (A*STAR)

Postdoctoral Researcher – Epigenetic Modifiers (Van Andel Research Institute)

Postdoctoral Fellowship – Cancer Biology (Massachusetts General Hospital Cancer Center/Harvard Medical School)

Postdoctoral Research Fellow – Metastatic Breast Cancer (Fred Hutchinson Cancer Research Center)

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