Mammary Cell News Volume 9.06 | Feb 16 2017

TOP STORY

Ovarian Hormones Awaken Newly Discovered Breast Stem Cells

Researchers have used advanced cellular, bioinformatics and imaging technology to reveal a long-lived type of stem cell in the breast that is responsible for the growth of the mammary glands during pregnancy. [Press release from the Walter and Eliza Hall Institute of Medical Research discussing online prepublication in Nature Cell Biology] Press Release | Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Induced p53 Loss in Mouse Luminal Cells Causes Clonal Expansion and Development of Mammary Tumors

The authors report that induced p53 loss in Krt8⁺ mammary luminal cells lead to their clonal expansion without directly affecting their luminal identity. Although p53 did not directly control the luminal fate, its loss facilitated acquisition of mammary stem cell-like properties by luminal cells and predisposed them to development of mammary tumors with loss of luminal identity. [Nat Commun] Full Article

Dub3 Inhibition Suppresses Breast Cancer Invasion and Metastasis by Promoting Snail1 Degradation

Scientists identified Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 was overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed epithelial–mesenchymal transition and decreased tumor cell migration, invasion, and metastasis. [Nat Commun] Full Article

MARK4 Inhibits Hippo Signaling to Promote Proliferation and Migration of Breast Cancer Cells

Investigators identified mammalian MARK family members as activators of YAP/TAZ. They showed that depletion of MARK4 in MDA-MB-231 breast cancer cells results in the loss of nuclear YAP/TAZ and decreases the expression of YAP/TAZ targets. [EMBO Rep] Abstract | Graphical Abstract

Automethylation of Protein Arginine Methyltransferase 7 and Its Impact on Breast Cancer Progression

Scientists demonstrated that R531 of protein arginine methyltransferase (PRMT)7 is self-methylated, both in vitro and in vivo. Automethylation of PRMT7 played a key role in inducing the epithelial-mesenchymal transition program and in promoting the migratory and invasive behavior of breast cancer cells. [FASEB J] Abstract

A Novel Orally Bioavailable Compound KPT-9274 Inhibits PAK4, and Blocks Triple Negative Breast Cancer Tumor Growth

The authors investigated a new clinical compound KPT-9274, which has been shown to inhibit PAK4 and NAMPT. They found that KPT-9274 (and its analog, KPT-8752) can reduce the steady state level of PAK4 protein in triple negative breast cancer cells. [Sci Rep] Full Article

The Mitotic Checkpoint Regulator RAE1 Induces Aggressive Breast Cancer Cell Phenotypes by Mediating Epithelial-Mesenchymal Transition

An in silico analysis of data retrieved from GENT and cBio-Portal identified ribonucleic acid export 1 (RAE1) upregulation in breast cancer tissues relative to normal breast cells. Functional studies of various cell lines showed that RAE1 induced invasive and migratory abilities by regulating epithelial-mesenchymal transition signals. [Sci Rep] Full Article

Stromal Fibroblasts Present in Breast Carcinomas Promote Tumor Growth and Angiogenesis through Adrenomedullin Secretion

Researchers showed that adrenomedullin (AM) and AM receptors mRNAs are highly expressed in cancer-associated fibroblasts (CAFs) prepared from invasive breast carcinoma when compared to normal fibroblasts. They showed that MCF-7 admixed with CAFs generated tumors of greater volume significantly different from the MCF-7 xenografts in nude mice due in part to the induced angiogenesis. Anti-AM receptors antibody and AM22-52 therapies significantly suppressed the growth of CAFs/MCF-7 tumors. [Oncotarget] Full Article

Pre-Clinical Evaluation of Small Molecule LOXL2 Inhibitors in Breast Cancer

Investigators tested the anti-tumor properties of two generations of novel small molecule lysyl oxidase-like 2 (LOXL2) inhibitor in the MDA-MB-231 human model of breast cancer. They confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. [Oncotarget] Full Article

CLINICAL RESEARCH

The BIG 2.04 MRC/EORTC SUPREMO Trial: Pathology Quality Assurance of a Large Phase III Randomized International Clinical Trial of Postmastectomy Radiotherapy in Intermediate-Risk Breast Cancer

SUPREMO is a Phase III randomized trial evaluating radiotherapy post-mastectomy for intermediate-risk breast cancer. 1688 patients were enrolled from 16 countries between 2006 and 2013. Scientists report the results of central pathology review carried out for quality assurance. [Breast Cancer Res Treat] Full Article

Hormonally Up-Regulated Neu-Associated Kinase: A Novel Target for Breast Cancer Progression

The authors focus on what is currently known about an under-studied protein kinase, and how targeting hormonally up-regulated neu-associated kinase may prove to be a potential therapeutic target for the treatment of breast cancer. [Pharmacol Res] Abstract | Graphical Abstract

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

TapImmune Advances TPIV 200 Phase II Triple-Negative Breast Cancer Trial after Favorable DSMB Safety Review

TapImmune, Inc. announced its lead cancer vaccine candidate, TPIV 200, received a positive recommendation from an independent Data Safety Monitoring Board (DSMB) to continue dosing triple-negative breast cancer patients in an ongoing Phase II clinical trial. [TapImmune, Inc.] Press Release

BriaCell Moves Forward to Initiate Phase I/IIa Clinical Study for BriaVaxTM in Advanced Breast Cancer

BriaCell Therapeutics Corp. announced that the company has submitted a Chemistry, Manufacturing, and Controls amendment which includes the details of extensive testing performed on BriaVax^™, the company’s proprietary vaccine for advanced breast cancer. Upon authorization by the FDA, the company plans to proceed with the initiation of the Phase I/IIa Clinical Study for BriaVax^™ in advanced breast cancer as previously announced. [BriaCell Therapeutics Corp.] Press Release

Scripps Florida Collaboration Awarded $3.3 Million to Develop Next-Generation Breast Cancer Therapies

A pair of scientists from the Florida campus of The Scripps Research Institute have been awarded up to $3.3 million from the National Cancer Institute of the National Institutes of Health to create the next generation of breast cancer treatments for the thousands of patients whose current treatment options are limited. [The Scripps Research Institute] Press Release

Henrietta Lacks’s Family Wants Compensation for Her Cells

The eldest son of Henrietta Lacks wants compensation from Johns Hopkins University and possibly others for the unauthorized use of her cells in research that led to decades of medical advances. The cells taken from the 31-year-old after she died of an aggressive form of cervical cancer in 1951 were the first to live outside the body in a glass tube. They were dubbed the HeLa cells and have become the most widely used human cells that exist in scientific research. [The Washington Post] Editorial

Broad Institute Wins Bitter Battle over CRISPR Patents

A panel of US Patent and Trademark Office judges have determined that a series of patents granted for CRISPR-Cas9 gene editing to the Broad Institute of MIT and Harvard will stand. [Nature News] Editorial

Ebola Funding Surge Hides Falling Investment in Other Neglected Diseases

Global funding for research on neglected diseases — which include tuberculosis, HIV/AIDS and malaria — is at its lowest level since 2007, according to the annual G-FINDER investment report by Policy Cures, a health-policy analysis firm in Sydney, Australia. [Nature News] Editorial

Robert F. Kennedy Jr. Says a ‘Vaccine Safety’ Commission Is Still in the Works

The vocal vaccine critic Robert F. Kennedy Jr. is still talking with President Donald Trump’s administration about establishing a commission to look into vaccine safety, Kennedy said at a press conference held at the National Press Club in Washington, D.C. [ScienceInsider] Editorial

NEW Stem Cell Summit
April 26-28, 2017
Boston, United States

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

NEW Senior Faculty Position – Epidemiology (Institute of Cancer Research)

NEW 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 Fellow – Breast Cancer Research (Gundersen Health System)

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

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

Postdoctoral Fellow – Breast Cancer (University of Hawaii Cancer Center)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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