Mammary Cell News Volume 11.27 | Jul 18 2019

TOP STORY

A Non-Canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer

Through an in vivo proximity-dependent labeling technique, researchers identified YAP1 and TEAD4 protein as co-regulators of ERα on enhancers. The binding of YAP1/TEAD4 to ERα-bound enhancers was augmented upon E₂ stimulation and was required for the induction of E₂/ERα target genes and E₂-induced oncogenic cell growth. [Mol Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Landscape of Transcriptomic Interactions between Breast Cancer and Its Microenvironment

To better understand tumor cell (TC)-tumor-adjacent cell (TAC) interactions, investigators computationally distinguished their transcriptomes in 1780 primary breast tumors. They showed that TC and TAC mRNA abundances were divergently associated with clinical phenotypes, including tumor subtypes and patient survival. [Nat Commun] Full Article

BRCA2 Abrogation Triggers Innate Immune Responses Potentiated by Treatment with PARP Inhibitors

Human cells in which BRCA2 expression was inhibited for four or 28 days were subjected to RNA-seq analyses revealing a biphasic response to BRCA2 abrogation. The early, acute response consists of downregulation of genes involved in cell cycle progression, DNA replication and repair was associated with cell cycle arrest in G1. [Nat Commun] Full Article

Single-Cell Analysis Reveals a Preexisting Drug-Resistant Subpopulation in the Luminal Breast Cancer Subtype

The authors performed extensive single-cell gene expression profiling of the luminal-type breast cancer cell line MCF7 and its derivatives, including docetaxel-resistant cells. Upregulation of EMT and stemness-related genes and downregulation of cell cycle-related genes, which were mainly regulated by LEF1, were observed in the drug-resistant cells. [Cancer Res] Abstract

Alterations in Wnt- and/or STAT3 Signaling Pathways and the Immune Microenvironment during Metastatic Progression

Scientists analyzed the cellular and molecular differences between primary tumors and paired lung metastases using a syngeneic p53-null mammary tumor model of basal-like breast cancer. Distinct subpopulations driven by the Wnt- and/or STAT3 signaling pathways were detected in vivo using a lentiviral Wnt- and STAT3 signaling reporter system. [Oncogene] Abstract

Mutant p53 Improves Cancer Cells’ Resistance to Endoplasmic Reticulum Stress by Sustaining Activation of the UPR Regulator ATF6

Researchers provided evidence that mutant p53 proteins could modulate the unfolded protein response (UPR) to increase cell survival upon endoplasmic reticulum stress, a condition to which cancer cells are exposed during tumor formation and progression, as well as during therapy. Mechanistically, this action of mutant p53 was due to enhanced activation of the pro-survival UPR effector ATF6, coordinated with inhibition of the pro-apoptotic UPR effectors JNK and CHOP. [Oncogene] Abstract

Long Non-Coding RNA LUCAT1/MiR-5582-3p/TCF7L2 Axis Regulates Breast Cancer Stemness via Wnt/β-Catenin Pathway

LncRNA LUCAT1 expression was assessed in breast cancer tissues by in situ hybridization. Sphere-formation assay and colony formation assay were used to detect cell self-renewal and proliferation, respectively. RNA immunoprecipitation, RNA pull down and luciferase reporter assays were used to identify LUCAT1 and TCF7L2 as the direct target of miR-5582-3p. [J Exp Clin Cancer Res] Full Article

The Kindlin2-p53-SerpinB2 Signaling Axis Is Required for Cellular Senescence in Breast Cancer

Investigators showed that Kindlin-2 regulated cellular senescence in part through its interaction with p53, whereby it regulated the expression of the p53-responsive genes; i.e., SerpinB2 and p21, during the induction of senescence. Their data showed that knockout of Kindlin-2 via CRISPR/Cas9 in several breast cancer cell lines significantly increased expression levels of both SerpinB2 and p21 resulting in the activation of hallmarks of cellular senescence. [Cell Death Dis] Full Article

A Sesquiterpenoid from Farfarae Flos Induces Apoptosis of MDA-MB-231 Human Breast Cancer Cells through Inhibition of JAK-STAT3 Signaling

Efficient separation methods and an MTT assay were conducted to isolate an anticancer compound from Farfarae Flos against triple negative breast cancer MDA-MB-231 cells. 7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone, a compound isolated from Farfarae Flos, showed a potent cytotoxic effect on MDA-MB-231 cells. [Biomolecules] Full Article

Proteogenomic Analysis of Protein Sequence Alterations in Breast Cancer Cells

The authors report the use of mass spectrometry for detecting the presence of mutations-missense, indels and frame shifts-in MCF7 and SKBR3 breast cancer, and non-tumorigenic MCF10A cells. The mutations were identified by expanding the database search process of raw mass spectrometry files by including an in-house built database of mutated peptides that complemented a minimally redundant, canonical database of Homo sapiens proteins. [Sci Rep] Full Article

Regulatory Mechanisms Leading to Differential Acyl-CoA Synthetase 4 Expression in Breast Cancer Cells

Scientists established for the first time that estrogen-related receptor alpha is a transcription factor involved in the higher activation of the human acyl-CoA synthetase 4 (ACSL4) promoter in breast cancer cells. Furthermore, a combination of inhibitors of ACSL4 and ERRα produced a synergistic decrease in MDA-MB-231 cell proliferation. [Sci Rep] Full Article

G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells

To investigate whether G0/G1 switch 2 (G0S2) affected invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. [Biomol Ther] Abstract

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Estrogen Receptor-Mediated Targeting of the Extracellular Matrix Network in Cancer

The coordinated actions of estrogen receptors (ERs) and extracellular matrix (ECM) macromolecules are principal mediators of ECM remodeling in the tumor and the adjacent stroma. In breast cancer, ERs are critical biomarkers as their expression in breast tumor determines the disease-free survival, yet guiding treatment decisions and predicting prognosis as well as response to endocrine therapy. [Semin Cancer Biol] Abstract

Breast Cancer: Occluded Role of Mitochondria N-Acetylserotonin/Melatonin Ratio in Co-Ordinating Pathophysiology

The author proposes that melatonergic pathway regulation within mitochondria provides an integrative framework for the wide array of data driving breast cancer pathophysiology. As melatonin is toxic to breast cancer cells, its production within mitochondria poses a significant challenge to breast cancer cell survival. [Biochem Pharmacol] Abstract

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Breast Cancer Patients to Have Further NICE-Approved Drug Combination Option on Cancer Drugs Fund

Another potentially life-extending drug combination for some people with advanced breast cancer will now be available on the Cancer Drugs Fund (CDF) following its approval by NICE in draft guidance published on July 17, 2019. The draft guidance recommends ribociclib used with fulvestrant as an option for people with hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer who have had previous endocrine therapy. [NICE 2019] Press Release

Breast Cancer Researcher to Receive Memorial Lecture Award

Joseph A. Sparano, MD, associate director for clinical research at Montefiore Einstein Center for Cancer Care at Albert Einstein Cancer Center, will receive the William L. McGuire Memorial Lecture Award at this year’s San Antonio Breast Cancer Symposium. [Healio] Press Release

The Plan to Mine the World’s Research Papers

Carl Malamud is on a crusade to liberate information locked up behind paywalls — and his campaigns have scored many victories. Now, the 60-year-old American technologist is turning his sights on a new objective: freeing paywalled scientific literature. And he thinks he has a legal way to do it. [Nature News] Editorial

Virologists Escorted out of Lab in Canada

Canada’s national police force is investigating “possible policy breaches” after researchers were escorted from a lab at Canada’s National Microbiology Laboratory in Winnipeg, CBC News reported. Prominent virologist Xiangguo Qiu, her colleague and husband Keding Cheng, and an unknown number of her students from China were removed from the lab. [The Scientist] Editorial

NEW EMBL Conference: Cancer Genomics
November 4-6, 2019
Heidelberg, Germany

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

NEW Research Officer – Tumor Progression in Breast and Prostate Cancer (Garvan Institute of Medical Research)

Scientific Officer – Breast Cancer Organoid/3D Cell Culture Facility (Institute of Cancer Research London)

Scientific Officer – Patient Derived Xenografts (Institute of Cancer Research)

Postdoctoral Fellowship – Redox Biology of Lung and Breast Cancer (Washington University School of Medicine)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

Canada Research Chair – Precision and Molecular Oncology (University of Calgary)

PhD Studentship – Molecular Mechanisms of Breast and Colorectal Cancers (Dalhousie University)

Postdoctoral Fellowship – Molecular Mechanisms of Breast and Colorectal Cancers (Dalhousie University)

Postdoctoral Fellow or Research Scientist – Cancer Biology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

Postdoctoral Associate – Cancer Immunology (The Jackson Laboratory)

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