Mammary Cell News Volume 9.04 | Feb 2 2017

TOP STORY

Identity and Dynamics of Mammary Stem Cells during Branching Morphogenesis

Scientists showed that morphogenesis is driven by proliferative terminal end buds that terminate or bifurcate with near equal probability, in a stochastic and time-invariant manner, leading to a heterogeneous epithelial network. They showed that the majority of terminal end bud cells function as highly proliferative, lineage-committed mammary stem cells that are heterogeneous in their expression profile and short-term contribution to ductal extension. [Nature] Abstract

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LABORATORY RESEARCH

Cellular Mechano-Environment Regulates the Mammary Circadian Clock

Researchers revealed that the breast epithelial clock is regulated by the mechano-chemical stiffness of the cellular microenvironment in primary cell culture. The mammary clock is controlled by the periductal extracellular matrix in vivo, which contributes to a dampened circadian rhythm during aging. [Nat Commun] Full Article | Press Release

Pharmacological Targeting of the Transcription Factor SOX18 Delays Breast Cancer in Mice

The authors used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. They described a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. [eLife] Full Article

Effective Personalized Therapy for Breast Cancer Based on Predictions of Cell Signaling Pathway Activation from Gene Expression Analysis

Investigators employed cell signaling pathway signatures to predict pathway activity in subtypes of MMTV-Myc mammary tumors. They split tumors into subsets and developed individualized combinatorial treatments for two subtypes with distinct pathway activation patterns. Their combinatorial therapy resulted in tumor regression, including regression in patient-derived xenograft samples from triple-negative breast cancer. [Oncogene] Abstract

The Cdc42/Rac1 Regulator CdGAP Is a Novel E-Cadherin Transcriptional Co-Repressor with Zeb2 in Breast Cancer

By using global gene expression approaches, researchers uncovered a novel function for Cdc42 GTPase-activating protein (CdGAP) in the regulation of expression of genes involved in epithelial-to-mesenchymal transition. They found that CdGAP used its proline-rich domain to form a functional complex with Zeb2 to mediate the repression of E-cadherin expression in ErbB2-transformed breast cancer cells. [Oncogene] Abstract

Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

The authors report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-breast cancer (BC) communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. [Cell Rep] Full Article | Graphical Abstract

Differentiation of Human Induced Pluripotent Stem Cells to Mammary-Like Organoids

Investigators developed a reliable two-step protocol to generate human mammary-like organoids from induced pluripotent stem cells (iPSCs). Non-neural ectoderm-cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. They then generated mammary-like organoids from 10-day mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. [Stem Cell Reports] Full Article | Graphical Abstract

SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24⁺ CD49f^hi Mammary Stem Cell-Enriched Compartment

The authors showed that the mammary stem cell (MaSC) population has a distinct SCA-1⁺ population that is abundant in pre-pubertal mammary glands. The SCA-1⁺ MaSCs have less stem cell markers and less in vivo repopulating activity than their SCA-1^neg counterparts. [Stem Cell Reports] Full Article | Press Release

Interplay between CCR7 and Notch1 Axes Promotes Stemness in MMTV-PyMT Mammary Cancer Cells

Scientists used a combination of molecular and cellular assays on primary mammary tumor cells from the MMTV-PyMT transgenic mouse with or without CCR7 to examine the signaling crosstalk between CCR7 and Notch pathways. They showed that CCR7 functionally intersects with the Notch signaling pathway to regulate mammary cancer stem-like cells. [Mol Cancer] Full Article

Osteoprotegerin Mediates Tumor-Promoting Effects of Interleukin-1beta in Breast Cancer Cells

Researchers used human breast cancer cell lines to investigate the effects of interleukin-1beta treatment on osteoprotegerin secretion as measured by ELISA. They report that interleukin-1beta induced osteoprotegerin secretion, independent of breast cancer subtype and basal osteoprotegerin levels. [Mol Cancer] Full Article

Inhibition of the Proteasome β2 Site Sensitizes Triple-Negative Breast Cancer Cells to β5 Inhibitors and Suppresses Nrf1 Activation

Investigators showed that clinically achievable inhibition of the β5 site of the proteasome by carfilzomib (Cfz) and bortezomib (Btz) does not result in loss of viability of triple-negative breast cancer cell lines. They used site-specific inhibitors and CRISPR-mediated genetic inactivation of β1 and β2 to demonstrate that inhibiting a second site of the proteasome, particularly the β2 site, sensitizes cell lines to Btz and Cfz in vitro and in vivo. [Cell Chem Biol] Abstract | Graphical Abstract

CLINICAL RESEARCH

Safety and Efficacy Study of Metronomic Vinorelbine, Cyclophosphamide plus Capecitabine in Metastatic Breast Cancer: A Phase II Trial

In a Phase II study scientists assessed the safety and efficacy of metronomic oral chemotherapy with vinorelbine, cyclophosphamide capecitabine in patients with metastatic breast cancer, either as first-line or second-line or greater therapy. Metronomic combination of cyclophosphamide, capecitabine and vinorelbine showed significant activity and good tolerability in patients hormonal receptor positive, metastatic breast cancer patients. [Cancer Lett] Abstract

Oncogenic Mechanisms of Lin28 in Breast Cancer: New Functions and Therapeutic Opportunities

The authors summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer. [Oncotarget] Full Article

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

Mayo Clinic to Test Vaccine Designed to Provide Immune Response against Early Breast Lesions

Keith Knutson, Ph.D., director of the Discovery and Translation Labs Cancer Research Program at Mayo Clinic’s campus in Florida, has received a $3.7 million grant from the U.S. Department of Defense to conduct a Phase II clinical trial that will test a vaccine designed to establish lifelong immunity against development of these precancerous lesions. [Mayo Clinic] Press Release

Perthera, Inc. Enters a Collaboration with Major Pharmaceutical Company to Identify Cancer Patients for Clinical Trials

Perthera, Inc. announced that Novartis will use Perthera’s unique cancer patient network to identify breast and lung cancer patients for targeted therapy trials. [Perthera, Inc.] Press Release

Trump Immigration Ban Upends International Work on Disease

Efforts to combat diseases rely on networks of scientists to detect outbreaks early, understand how the diseases operate and then intervene. Researchers say that President Donald Trump’s travel ban challenges that process, putting the United States at risk. [Nature News] Editorial

On 22 April, Empiricists around the Country Will March for Science

The grassroots team coordinating the March for Science on Washington, D.C., have now set a date: 22 April. And they are inviting organizers in cities around the world to lead parallel demonstrations. [ScienceInsider] Editorial

NEW AACR Annual Meeting 2017
April 1-5, 2017
Washington, D.C., United States

NEW hPSC Training Course: Reprogramming, Maintenance and Reversion to Naive-Like State
April 24-26, 2017
Vancouver, Canada

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

NEW Postdoctoral Positions – Molecular Cancer Research (University of Copenhagen)

Postdoctoral Fellow – Breast Cancer Research (Gundersen Health System)

Postdoctoral Researcher – Breast Cancer Epidemiology (Karolinska Institutet)

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)

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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