Mammary Cell News Volume 11.09 | Mar 14 2019

TOP STORY

Stress Hormones Promote Breast Cancer Metastasis

Scientists have deciphered the molecular mechanisms linking breast cancer metastasis with increased stress hormones. In addition, they found that synthetic derivatives of stress hormones, which are frequently used as anti-inflammatory in cancer therapy, decrease the efficacy of chemotherapy. [Press release from University of Basel discussing online prepublication in Nature] Press Release | Abstract

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LSECtin on Tumor-Associated Macrophages Enhances Breast Cancer Stemness via Interaction with Its Receptor BTN3A3

Admixture of LSECtin-positive macrophages increased the tumorigenic activity of breast cancer cells dependent on BTN3A3. Disruption of the LSECtin-BTN3A3 axis with BTN3A3-Fc or anti-BTN3A3 mAb had a therapeutic effect on breast cancer. [Cell Res] Abstract

Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment

In a humanized model of spontaneous breast cancer metastasis to bone, Anakinra or canakinumab reduced metastasis and reduced the number of tumor cells shed into circulation. Production of IL1B by tumor cells promoted epithelial-to-mesenchymal transition, invasion, migration, and bone colonization. [Clin Cancer Res] Abstract

Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling

Free fatty acids (FFA) activated both the estrogen receptor alpha (ERα) and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1, which targeted ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. [Cancer Res] Abstract | Press Release

Randomly Distributed K14+ Breast Tumor Cells Polarize to the Leading Edge to Direct Collective Migration in Response to Chemical and Mechanical Environmental Cues

Prior to migration, breast tumor leader cells (K14+) were present throughout a tumor organoid and migrated to the leading edge in response to biochemical and biomechanical cues. Impairment of either CXCR4 or the collagen receptor DDR2 abrogated polarization of leader cells and directed collective migration. [Cancer Res] Abstract

FOXM1 Deubiquitination by USP21 Regulates Cell Cycle Progression and Paclitaxel Sensitivity in Basal-Like Breast Cancer

Investigators identified USP21 in an RNAi-based screen for deubiquitinases that controlled FOXM1 abundance. USP21 increased the stability of FOXM1, and USP21 bound and deubiquitinated FOXM1 in vivo and in vitro, indicating a direct enzyme-substrate relationship. [Cell Rep] Full Article | Press Release | Graphical Abstract

Characterization of Triple-Negative Breast Cancer Preclinical Models Provides Functional Evidence of Metastatic Progression

The authors describe two preclinical spontaneously metastatic triple-negative breast cancer orthotopic murine models for the development of advanced therapeutics: an immunodeficient human MDA-MB-231-Luc model and an immunocompetent mouse 4T1 model. [Int J Cancer] Abstract

Intracellular Citrate Accumulation by Oxidized ATM-Mediated Metabolism Reprogramming via PFKP and CS Enhances Hypoxic Breast Cancer Cell Invasion and Metastasis

Researchers found that hypoxia induced DNA damage-independent ATM activation and suppression of oxidized ATM reduced intracellular citrate via decreasing the levels of phosphofructokinase (PFKP) and citrate synthase (CS), two key glucose metabolism-associated enzymes. [Cell Death Dis] Full Article

The LXR-623-Induced Long Non-Coding RNA LINC01125 Suppresses the Proliferation of Breast Cancer Cells via PTEN/AKT/p53 Signaling Pathway

LINC01125 knockdown resulted in the inhibition of the cytotoxic effect of LXR-623; in contrast, LINC01125 overexpression significantly enhanced the effect of LXR-623. LXR-623 and LINC01125-mediated anti-growth regulation was, at least in part, associated with the participation of the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT)/mouse double minute 2 homolog/p53 pathway. [Cell Death Dis] Full Article

Water-Responsive Hybrid Nanoparticles Codelivering ICG and DOX Effectively Treat Breast Cancer via Hyperthermia-Aided DOX Functionality and Drug Penetration

Phospholipid-calcium-carbonate hybrid nanoparticles exhibited satisfactory stability against various aqueous environments with minimal drug leakage and could readily decompose to facilitate quick drug release into cancer cells. [Adv Healthc Mater] Abstract

The Emerging Role of Xanthine Oxidase Inhibition for Suppression of Breast Cancer Cell Migration and Metastasis Associated with Hypercholesterolemia

In vitro, febuxostat (FBX) significantly inhibited LDL-induced reactive oxygen species production and cell migration. Treatment of small interfering RNA against xanthine oxidase was consistent with the findings of FBX treatment. [FASEB J] Abstract

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S-Nitrosylation and Its Role in Breast Cancer Angiogenesis and Metastasis

In the tumor environment, the role of S-nitrosylation in the endothelium has not been addressed; however, the evidence demonstrates that S-nitrosylation of endothelial proteins may regulate angiogenesis, adhesion of tumor cells to the endothelium, intra and extravasation of tumor cells and contribute to metastasis. [Nitric Oxide] Abstract

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Sermonix to Present on Potential for Lasofoxifene in Metastatic Breast Cancer Treatment

Sermonix Pharmaceuticals LLC announced that founder and Chief Executive Officer Dr. David Portman will present. Dr. Portman will discuss the Phase II study of its lead investigational drug, lasofoxifene, and the drug’s potential as a novel precision medicine treatment for metastatic breast cancer patients with an ESR1 mutation identified through a liquid biopsy. [Press release from Sermonix Pharmaceuticals LLC (GlobeNewswire, Inc.) discussing research to be presented at the Boston Oncology Investor Conference, Boston] Press Release

Atossa Genetics Announces FDA Approval of Oral Endoxifen for “Expanded Access” as Post-Mastectomy Treatment for a US Breast Cancer Patient

Atossa Genetics Inc. announced that the FDA has issued a “Safe to Proceed” letter under their “expanded access” program permitting the use of Atossa’s oral Endoxifen as a post-mastectomy treatment in a pre-menopausal, estrogen-receptor positive breast cancer patient. [Atossa Genetics, Inc.] Press Release

Infinity to Initiate MARIO-3, a Phase II Multi-Arm Study Evaluating IPI-549 in Front-Line Triple Negative Breast Cancer and Renal Cell Cancer

Infinity Pharmaceuticals, Inc. announced that it has entered into a master clinical supply agreement under which Roche will supply atezolizumab to Infinity for use in MARIO-3, a Phase II multi-arm combination cohort study. [Infinity Pharmaceuticals, Inc.] Press Release

CytoDyn Reports Significant Reduction in Breast Cancer Tumor Metastasis in Preclinical Study and Requests FDA Fast Track Designation for Leronlimab (PRO 140) in Metastatic-Triple Negative Breast Cancer (mTNBC)

CytoDyn Inc. announced that leronlimab, its lead investigational CCR5 inhibitor, showed significant reduction in the volume of human breast cancer tumor metastasis in a murine xenograft model. The metastatic tumor volume was reduced by more than 98% after 7 weeks. [CytoDyn, Inc.] Press Release

Roche’s VENTANA PD-L1 (SP142) Assay Approved as First Companion Diagnostic to Identify Triple-Negative Breast Cancer Patients Eligible for Treatment with Tecentriq in Combination with Abraxane

Roche announced US Food and Drug Administration approval of the VENTANA PD-L1 Assay as the first companion diagnostic to aid in identifying triple-negative breast cancer patients eligible for treatment with the Roche cancer immunotherapy Tecentriq^® plus chemotherapy. [Roche Group] Press Release

In a First, US Private Sector Employs Nearly as Many PhDs as Schools Do

The job market for US science and engineering PhDs is about to pass a long-anticipated milestone. For decades, educational institutions have been the largest employer of PhDs. In 1997, for instance, they eclipsed private sector employment by 11 percentage points, according to the US National Science Foundation’s biennial Survey of Doctorate Recipients. [ScienceInsider] Editorial

Adopt a Moratorium on Heritable Genome Editing

Scientists call for a global moratorium on all clinical uses of human germline editing — that is, changing heritable DNA (in sperm, eggs or embryos) to make genetically modified children. [Nature News] Editorial

NEW Advanced Cell Therapies and Tissue Engineering
November 14-16, 2019
Milan, Italy

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NEW Professor – Breast Cancer (University Hospitals Cleveland Medical Center)

NEW Postdoctoral Researcher – BRCA1/2-Deficient Tumors (University of Oxford)

Postdoctoral Scientist – Breast Tumor Suppressor BRCA1 in DNA Repair (The George Washington University)

Postdoctoral Associate – Cancer Immunology (The Jackson Laboratory)

Scientific Review Officer – Breast Cancer (METAvivor)

Faculty Position – Breast Cancer Research (The Mayo Clinic)

Postdoctoral Fellow – Cancer Bioinformatics (BC Cancer Research Center, PHSA)

Postdoctoral Fellowship – Breast Cancer (Providence John Wayne Cancer Institute)

International Scientific Director – Breast Cancer (Roche)

Postdoctoral Fellowship – Cancer Research (North Carolina Central University)

Postdoctoral Fellow – Breast Cancer Research (City of Hope)

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