Mammary Cell News Volume 11.26 | Jul 11 2019

TOP STORY

An ErbB2/c-Src Axis Links Bioenergetics with PRC2 Translation to Drive Epigenetic Reprogramming and Mammary Tumorigenesis

Using multiple models of breast cancer driven by the oncogene ErbB2, the authors showed that the tyrosine kinase c-Src linked energy sufficiency with polycomb repressor complex 2 (PRC2) overexpression via control of mRNA translation. By stimulating mitochondrial ATP production, c-Src suppressed energy stress, permitting sustained activation of the mammalian/mechanistic target of rapamycin complex 1, which increased the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. [Nat Commun] Full Article

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Uncovering the Signaling Landscape Controlling Breast Cancer Cell Migration Identifies Novel Metastasis Driver Genes

Investigators applied an imaging-based RNAi phenotypic cell migration screen using two highly motile triple-negative breast cancer (TNBC) cell lines to provide a repository of signaling determinants that functionally drove TNBC cell motility. They screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which were linked to signaling networks predictive for breast cancer progression. [Nat Commun] Full Article

Downregulation of FOXO3a by DNMT1 Promotes Breast Cancer Stem Cell Properties and Tumorigenesis

Researchers report that DNMT1-mediated FOXO3a promoter hypermethylation led to downregulation of FOXO3a expression in breast cancer. FOXO3a was functionally related to the inhibition of FOXM1/SOX2 signaling and to the consequent suppression of breast cancer stem cell properties and tumorigenicity. [Cell Death Differ] Full Article

Loss of Slug Compromises DNA Damage Repair and Accelerates Stem Cell Aging in Mammary Epithelium

Scientists showed that Slug facilitated efficient execution of RPA32-mediated DNA damage response signaling. Slug deficiency led to delayed phosphorylation of ataxia telangiectasia mutated and Rad3-related protein and its effectors RPA32 and CHK1. [Cell Rep] Full Article | Graphical Abstract

Development of Functional Dendrisomes Based on a Single Molecule of Polyesterbenzylether Dendrimer and Their Application in Cancer Stem Cell Therapy

Investigators report a type of functional dendrisomes constructed by the synthesized amphiphilic dendrimers, which enhanced cellular uptake by breast cancer stem cells (CSCs), differentiated breast CSCs by carrying all-trans retinoic acid (ATRA), and increased the anticancer efficacy by carrying ATRA and docetaxel in vitro and in breast cancer-bearing mice. [NPG Asia Mater] Full Article

Septin 9 Isoforms Promote Tumorigenesis in Mammary Epithelial Cells by Increasing Migration and ECM Degradation through Metalloproteinase Secretion at Focal Adhesions

Researchers over-expressed several of its isoforms in breast cancer cell lines. Global transcriptomic profiling supported a role of Septin 9 in invasion. [Oncogene] Abstract

KIAA1429 Acts as an Oncogenic Factor in Breast Cancer by Regulating CDK1 in an N6-Methyladenosine-Independent Manner

Scientists found KIAA1429 was highly expressed in breast cancer tissues, but frequently down-regulated in non-cancerous breast tissues. The overall survival of breast cancer patients with high-expression KIAA1429 was significantly shorter than those with low-expression KIAA1429. [Oncogene] Abstract

Metformin Mediates Induction of miR-708 to Inhibit Self-Renewal and Chemoresistance of Breast Cancer Stem Cells through Targeting CD47

The authors evaluated the role of mi-708 and metformin in breast breast cancer stem cells (BCSCs), and found that the expression of miR‐708 was significantly down-regulated in BCSCs and tumor tissues, and correlated with chemotherapy response and prognosis. Moreover, miR-708 markedly inhibited sphere formation, CD44⁺/CD24⁻ ratio, and tumor initiation and increased chemosensitivity of BCSCs. [J Cell Mol Med] Full Article

Depletion of Ras Suppressor-1 (RSU-1) Promotes Cell Invasion of Breast Cancer Cells through a Compensatory Upregulation of a Truncated Isoform

Investigators used non-invasive MCF-7 cells, expressing only RSU-1L, and highly invasive MDA-MB-231-LM2 expressing both isoforms and generated stable shRNA-transduced cells lacking RSU-1L, while the truncated RSU-1-X1 isoform was depleted by siRNA-mediated silencing. [Sci Rep] Full Article

Matrix Stiffness Induces a Tumorigenic Phenotype in Mammary Epithelium through Changes in Chromatin Accessibility

Researchers found that increased stiffness yielded cells with more wrinkled nuclei and with increased lamina-associated chromatin, that cells cultured in stiff matrices displayed more accessible chromatin sites, which exhibited footprints of Sp1 binding, and that this transcription factor acted along with the histone deacetylases 3 and 8 to regulated the induction of stiffness-mediated tumorigenicity. [Nat Biomed Eng] Abstract

Molecular Mechanism of Forkhead Box M1 Inhibition by Thiostrepton in Breast Cancer Cells

Experimental studies were designed to examine the effectiveness of thiostrepton in downregulating Forkhead box M1 mRNA expression and activity, leading to senescence and apoptosis of breast cancer cells. The cytotoxicity of thiostrepton in breast cancer was determined using cell viability assay. [Oncol Rep] Abstract

Knockdown of FAM64A Suppresses Proliferation and Migration of Breast Cancer Cells

The expression of FAM64A mRNA in breast cancer samples was determined by RT-qPCR assay and TCGA database mining. Kaplan-Meier plotter was used to analyze whether FAM64A expression impacted prognosis. Then, the expression of FAM64A was silenced using RNA interference. [Breast Cancer] Abstract

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Ductal Carcinoma In Situ: To Treat or Not to Treat, That Is the Question

Currently, all ductal carcinoma in situ (DCIS) lesions are treated, and treatment comprises either mastectomy or breast-conserving surgery supplemented with radiotherapy. However, most DCIS lesions remain indolent. Difficulty in discerning harmless lesions from potentially invasive ones can lead to over-treatment of this condition in many patients. [Br J Cancer] Full Article

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Atossa Genetics Announces New Proprietary Modified-Release Oral Endoxifen Tablet; Phase I Clinical Trial Initiated

Atossa Genetics Inc. announced that it is developing a new proprietary modified-release oral tablet form of its Endoxifen, which is the form of the drug that the company intends for future clinical studies and commercialization. [Atossa Genetics Inc.] Press Release

Lothar Lilge Recognized with 2019 Lifetime Achievement Award at 17^th World Congress of the International Photodynamic Association

Dr. Lothar Lilge of University of Toronto, Canada was the recipient of the 2019 Lifetime Achievement Award. Dr. Lilge’s extensive photodynamic therapy (PDT) experience which spans 27 years, includes basic science, pre-clinical and clinical work in all areas of photodynamic therapy including photodiagnosis, breast, bladder and brain cancer related PDT, vascular PDT and antimicrobial PDT. [The 17^th World Congress of the International Photodynamic Association (GlobeNewswire, Inc.)] Press Release

Sweden Passes Law For National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

As Visa Difficulties Persist, Scientists Push for Change

Individual researchers and science societies are finding solutions so colleagues around the globe can attend conferences, from remote presentations to relocating conferences. [The Scientist] Editorial

NEW 2019 National Cancer Research Institute Cancer Conference
November 3-5, 2019
Glasgow, United Kingdom

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

NEW 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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