Mammary Cell News Volume 9.08 | Mar 2 2017

TOP STORY

Newly Discovered Vulnerability in an Aggressive Breast Cancer Provides Therapeutic Target

Most women with triple-negative breast cancer (TNBC) do not respond to broadly-targeted chemotherapies, and those who do often develop resistance to the drugs. Investigators have discovered a vulnerability that offers a new strategy to combat TNBC. [Press release from the Beth Israel Deaconess Medical Center discussing online prepublication in Cancer Discovery] Press Release | Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Vitamin D Receptor Regulates Autophagy in the Normal Mammary Gland and in Luminal Breast Cancer Cells

The authors document that the vitamin D receptor (VDR) acts as a master transcriptional regulator of autophagy. Activation of the VDR by vitamin D induced autophagy and an autophagic transcriptional signature in breast cancer (BC) cells that correlated with increased survival in patients; strikingly, this signature was present in the normal mammary gland and was progressively lost in patients with metastatic BC. [Proc Natl Acad Sci USA] Abstract

miR-600 Acts as a Bimodal Switch that Regulates Breast Cancer Stem Cell Fate through WNT Signaling

Investigators performed two microRNA (miRNA) gain- and loss-of-function screens to identify miRNAs that regulate the choice between breast cancer stem cell (bCSC) self-renewal and differentiation. They found that miR-600 silencing results in bCSC expansion, while its overexpression reduces bCSC self-renewal, leading to decreased in vivo tumorigenicity. [Cell Rep] Full Article | Graphical Abstract

Sulforaphane Enhances the Anticancer Activity of Taxanes against Triple Negative Breast Cancer by Killing Cancer Stem Cells

Researchers examined the combination of taxanes with a breast cancer stem cell (CSC)-targeting agent sulforaphane for use against triple negative breast cancer (TNBC). They demonstrated that paclitaxel or docetaxel treatment induces IL-6 secretion and results in expansion of CSCs in TNBC cell lines. [Cancer Lett] Abstract

Mechanical Compression Induces VEGFA Overexpression in Breast Cancer via DNMT3A-Dependent miR-9 Downregulation

Scientists demonstrated that compression enhances a tumor progression phenotype using an in vitro compression model, and validated the results from the in vitro model with high- and low-compressed breast cancer tissues. [Cell Death Dis] Full Article

Molecular Analysis of BRCA1 in Human Breast Cancer Cells under Oxidative Stress

Researchers used a combination of molecular imaging and biochemical tools to study the properties of the breast cancer susceptibility protein (BRCA)1 in human cancer cells. Their results reveal new information for the manner in which full-length BRCA1 engages its binding partner, the BRCA1-associated ring domain protein, under oxidative stress conditions. [Sci Rep] Full Article | Press Release

Fatty Acid Synthase Regulates Estrogen Receptor-α Signaling in Breast Cancer Cells

Using pharmacological and genetic approaches, investigators assessed the molecular relationship between fatty acid synthase (FASN) signaling and estrogen receptor alpha (ERα) signaling in breast cancer. The small compound C75, a synthetic slow-binding inhibitor of FASN activity, induced a dramatic augmentation of estradiol-stimulated, ERα-driven transcription. [Oncogenesis] Full Article

Proximity of Metastatic Cells Enhances Their Mechanobiological Invasiveness

Scientists previously showed that single metastatic breast-cancer cells will mechanically indent a synthetic, impenetrable polyacrylamide gel with physiological-stiffness in attempted invasion; benign breast cells did not indent the gels. In solid tumors, e.g., breast cancers, metastases occur predominantly by collective cell-invasion. They evaluated the effects of cell proximity on mechanical invasiveness, specifically through changes in gel indention. [Ann Biomed Eng] Abstract

Human Brain Metastatic Stroma Attracts Breast Cancer Cells via Chemokines CXCL16 and CXCL12

Through RNA-Seq and protein analyses, the authors found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast. [NPJ Breast Cancer] Full Article

Antitumor Effects of Naturally Occurring Cardiac Glycosides Convallatoxin and Peruvoside on Human ER⁺ and Triple-Negative Breast Cancers

Researchers aimed to evaluate anticancer effects of two naturally occurring cardiac glycosides, convallatoxin (CT) and peruvoside (PS), on ER⁺ and triple-negative breast cancers (TNBCs) cells. CT and PS demonstrated dose- and time-dependent cytotoxic effect on MCF-7 cells, which was further supported by loss of colony formation on drug treatment. [Cell Death Discov] Full Article

Mammary Adipocytes Stimulate Breast Cancer Invasion through Metabolic Remodeling of Tumor Cells

In tumor cell lines, scientists demonstrated that free fatty acids can be released over time from lipid droplets through an adipose triglyceride lipase (ATGL)-dependent lipolytic pathway. In vivo, ATGL was expressed in human tumors where its expression correlated with tumor aggressiveness and was upregulated by contact with adipocytes. [JCI Insight] Full Article

Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain N-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs

The authors critically analyze reports investigating the ability of long-chain n-3 polyunsaturated fatty acids (PUFA) to modulate the Ras/ERK and the phosphoinositide survival signaling pathways often aberrantly activated in breast cancer and representing the main targets of innovative therapies. [Nutrients] Full Article | Graphical Abstract

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

Oncolytics Biotech^® Inc. Announces Canadian Cancer Trials Group to Present Final Randomized Data from Phase II Metastatic Breast Cancer Study

Oncolytics Biotech^® Inc. announced that the Canadian Cancer Trials Group will present clinical trial data evaluating the company’s investigational immuno-oncology viral-agent, REOLYSIN^®. [Press release from Oncolytics Biotech^® Inc. discussing research to be presented at the American Academy of Cancer Research (AACR) Annual Meeting, Washington, DC.] Press Release

Amaran Biotechnology Selects Stellar KLH for Cancer Vaccines

Stellar Biotechnologies, Inc. and Amaran Biotechnology, Inc. have entered into an exclusive multi-year supply agreement in connection with clinical development studies of immunotherapies for metastatic breast cancer and other cancers. [Stellar Biotechnologies, Inc.] Press Release

Phase III APHINITY Study Shows Roche’s Perjeta® Regimen Helped People with an Aggressive Type of Early Breast Cancer Live Longer without Their Disease Returning Compared to Herceptin^® and Chemotherapy

Roche, the Breast International Group, Breast European Adjuvant Study Team and Frontier Science Foundation announced positive results from the Phase III APHINITY study. The study met its primary endpoint and showed that adjuvant treatment with the combination of Perjeta^®, Herceptin^® and chemotherapy achieved a statistically significant reduction in the risk of recurrence of invasive disease or death in people with HER2-positive early breast cancer compared to Herceptin and chemotherapy alone. [Roche] Press Release

Rexahn Pharmaceuticals Doses First Patient in a Phase IIa Trial of Supinoxin^™ in Patients with Metastatic Triple Negative Breast Cancer

Rexahn Pharmaceuticals, Inc. announced that it has begun enrolling patients into a Phase IIa clinical study of Supinoxin^™ in metastatic triple negative breast cancer (TNBC). The study will evaluate the safety and efficacy of Supinoxin^™ in patients with metastatic TNBC who have failed prior treatments. [Rexahn Pharmaceuticals, Inc.] Press Release

NIH Awards CSUN Professor $1.46 Million to Support Breast, Pancreatic Cancer Research

The National Institutes of Health has awarded California State University, Northridge biology professor Jonathan Kelber $1.46 million over the next four years to support his research group in their ongoing studies of the cancer “support wall” gene called PEAK1. His research has implications for future treatment diagnosis and treatment practices for breast and pancreatic cancer patients. [California State University, Northridge] Press Release

Senior Republican Lawmaker Has Some Advice for U.S. Science Marchers

The chairman of a congressional spending panel that oversees a wide swath of U.S. science agencies has some unusual advice for scientists planning to march on 22 April: Don’t talk about research. Instead, demand that Congress find a way to cut mandatory spending programs. [ScienceInsider] Editorial

UK Scientists Welcome Changes to Controversial Research Reforms

Amendments aim to protect autonomy and the independence of research funders from political interference. [Nature News] Editorial

Trump’s 2018 Budget Will Squeeze Civilian Science Agencies

The chunk of the federal budget that includes most of the U.S. government’s spending on basic science would shrink by 10.5% in 2018 under a plan outlined by President Donald Trump and administration officials. [ScienceInsider] Editorial

NEW AACR International Conference on Translational Cancer Medicine
May 4-6, 2017
Sao Paulo, Brazil

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

NEW Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine)

Postdoctoral Fellow – Estrogen Receptor Positive Breast Cancer (AstraZeneca)

Senior Faculty Position – Epidemiology (Institute of Cancer Research)

Cancer Bioinformatician – Breast Cancer (Institute of Cancer Research)

Assistant or Associate Professor – Breast Cancer (Roswell Park Cancer Institute)

Postdoctoral Positions – Molecular Cancer Research (University of Copenhagen)

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

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

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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