Mammary Cell News Volume 11.38 | Oct 3 2019

TOP STORY

The CXCL5/CXCR2 Axis Is Sufficient to Promote Breast Cancer Colonization during Bone Metastasis

Researchers developed an ex vivo co-culture method to grow cancer cells in mouse bones to assess cancer cell proliferation using healthy or cancer-primed bones. Profiling soluble factors from conditioned media identified the chemokine CXCL5 as a candidate to induce metastatic colonization. [Nat Commun] Full Article

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Targeting PML in Triple Negative Breast Cancer Elicits Growth Suppression and Senescence

Investigators demonstrated that triple negative breast cancer cells were addicted to the expression of promyelocytic leukemia protein (PML). PML inhibition led to a remarkable growth arrest combined with features of senescence in vitro and in vivo. Mechanistically, the growth arrest and senescence were associated to a decrease in MYC and PIM1 kinase levels, with the subsequent accumulation of CDKN1B (p27), a trigger of senescence. [Cell Death Differ] Full Article

Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer

The authors showed that GLS2 expression was elevated by GATA3 in luminal-subtype cells but suppressed by promoter methylation in basal-subtype cells. Although luminal breast cancers resisted GLS-selective inhibitors, they found that they could be targeted with a dual-GLS/GLS2 inhibitor. [Cell Rep] Full Article | Graphical Abstract

Identification of FUBP1 as a Long Tail Cancer Driver and Widespread Regulator of Tumor Suppressor and Oncogene Alternative Splicing

Scientists identified far upstream binding protein 1 (FUBP1) as an ‘long tail’ driver using an in vivo CRISPR screen. FUBP1 cooperated with other tumor suppressor genes to transform mammary epithelial cells by disrupting cellular differentiation and tissue architecture. [Cell Rep] Full Article | Graphical Abstract

Glyphosate Primes Mammary Cells for Tumorigenesis by Reprogramming the Epigenome in a TET3-Dependent Manner

Combining glyphosate with enhanced expression of microRNA 182-5p associated with breast cancer induced tumor development in 50% of mice. Culture of primary cells from resected tumors revealed a luminal B phenotype in response to glyphosate-miR182–5p exposure with sensitivity to tamoxifen and invasive and migratory potentials. [Front Genet] Full Article

An Increased Cell Cycle Gene Network Determines MEK and Akt Inhibitor Double Resistance in Triple-Negative Breast Cancer

Using genomic, transcriptomic and proteomic datasets of these triple negative breast cancer (TNBC) cell lines researchers unraveled molecular features associated with the MEK and Akt drug resistance. MEK inhibitor-resistant TNBC cell lines were discriminated from Akt inhibitor-resistant lines by the presence of PIK3CA/PIK3R1/PTEN mutations, high p-Akt and low p-MEK levels, yet these features could not distinguish double-resistant cells. [Sci Rep] Full Article

Increase in Fatty Acids and Flotillins upon Resveratrol Treatment of Human Breast Cancer Cells

Investigators studied the relationship between the formation of lipid rafts and the expression of flotillins and lipids in human breast cancer cells. They used the polyphenol compound resveratrol to alter the structure and function of the plasma membrane. [Sci Rep] Full Article

EGF Receptor Stimulation Shifts Breast Cancer Cell Glucose Metabolism toward Glycolytic Flux through PI3 Kinase Signaling

The authors explored the cellular mechanism and signaling pathways that could explain the relation between epidermal growth factor recepotr (EGFR) and breast cancer cell glucose metabolism. ^8F-fluorodeoxyglucose uptake, lactate production and hexokinase activity were measured, and proliferation assays and western blots were performed. [PLoS One] Full Article

Interaction of Tumor Cells and Astrocytes Promotes Breast Cancer Brain Metastases through TGF-β2/ANGPTL4 Axes

The combination of microarray analysis, qPCR, and ELISA assay were carried out to demonstrate the astrocyte-conditioned medium-induced expression of angiopoietin-like 4 (ANGPTL4) in triple negative breast cancer cells. A stable ANGPTL4-knockdown MDA-MB-231 cell line was generated by ANGPTL4 short-hairpin RNA and inoculated into mice via left ventricular injection to evaluate the role of ANGPTL4 in brain metastasis formation. [npj Precis Oncol] Full Article

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Breast Cancer

On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2, activation of hormone receptors and/or BRCA mutations. Treatment strategies differ according to molecular subtype. [Nat Rev Dis Primers] Full Article

Potential Role of MSC/Cancer Cell Fusion and EMT for Breast Cancer Stem Cell Formation

The authors discuss several possible scenarios that are not mutually exclusive but may even act synergistically: fusion of cancer cells with mesenchymal stem cells (MSCs) to yield hybrid cells and/or the induction of epithelial-mesenchymal transition in breast cancer cells by MSCs, which can relay signals for retrodifferentiation and eventually, the generation of breast cancer stem cells. [Cancers] Full Article

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Novartis Kisqali^® Delivers Consistently Superior Overall Survival – MONALEESA-3 Trial Demonstrates More Life for Postmenopausal HR⁺/HER^2- Advanced Breast Cancer Patients

Novartis announced results from the MONALEESA-3 trial, which showed Kisqali^® achieved statistically significant improvement in overall survival. This is the second Phase III trial in which Kisqali combination therapy met the secondary endpoint of overall survival at the pre-planned interim analysis. [Novartis] Press Release

CytoDyn Treats First Patient in Phase Ib/II Clinical Trial with Leronlimab (PRO 140) for Patients with Treatment-Naïve, Metastatic Triple-Negative Breast Cancer

CytoDyn Inc. a CCR5 antagonist with the potential for multiple therapeutic indications announced the injection of the first patient in a Phase Ib/II clinical protocol with treatment-naïve metastatic triple-negative breast cancer. [CytoDyn Inc.] Press Release

Atossa Genetics Announces Preliminary Results from Phase I Study of Modified-Release Tablet Oral Endoxifen

Atossa Genetics Inc. reported preliminary results from its Phase I study of its proprietary modified-release tablet form of oral Endoxifen. There were no unexpected and serious adverse events; no clinically significant adverse safety signals; and no clinically significant adverse events in participants receiving the tablet form of oral Endoxifen. [Atossa Genetics Inc.] Press Release

R01 Grant Funds Research Examining Small RNAs in Metastatic Breast Cancer

Xiaoting Zhang, PhD, professor of cancer biology at the University of Cincinnati College of Medicine, received federal funding, an R01 grant from the National Cancer Institute, to study certain genetic material, known as small RNAs, in breast cancer metastasis. [The University of Cincinnati (EurekAlert)] Press Release

Split Decisions: How Brexit Has Taken a Toll on Five Researchers

On 23 June 2016, 34 million UK citizens took to the polls to vote on a simple, fateful question: Should the United Kingdom remain a part of the European Union, or should it leave? Nearly 52%—a majority of 1.3 million—wanted out, and conservative politicians vowed to carry out the people’s wishes. [ScienceInsider] Editorial

Trump Set to Nominate Stephen Hahn as FDA Commissioner, Pending Vetting Process

President Trump is set to nominate Dr. Stephen Hahn to lead the FDA, pending completion of the vetting process, according to two people familiar with the selection process. Hahn, an oncologist, is the chief medical executive at MD Anderson Cancer Center in Houston. [STAT News] Editorial

Human Reference Genome Doesn’t Capture Full Genetic Diversity

It’s hard to study genetic sequences if they’re absent from the human reference genome, the product of the $2.7 billion Human Genome Project, which is typically used as a guide for genomic studies. A new study has identified more than 61,000 novel genetic sequences across 1,000 Swedish genomes that are absent from the human reference genome. [The Scientist] Editorial

NEW AACR-KCA Joint Workshop on Precision Medicine
November 14-15, 2019
Seoul, Korea

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NEW Chief Editor – Nature Ageing (Nature Research)

Postdoctoral Position – Cancer Biology (Memorial Sloan Kettering Cancer Center)

Research Scientist – Breast Cancer (The University of Pittsburgh)

Postdoctoral Researcher – Nanomedicine and Immunoengineering (University of California San Diego)

Postdoctoral Research Fellow – Epithelial Growth in Development and Cancer (Fred Hutchinson Cancer Research Center)

Project Scientist – Breast and Hematological Tumors (Cedars-Sinai)

Postdoctoral Research Scientist – Role of Cancer-Associated Fibroblast Metabolism in Breast Cancer (Cancer Research UK Beatson Institute)

Postdoctoral Fellow – Breast and Prostate Cancer (Mayo Clinic Comprehensive Cancer Center)

Research Assistant – Endocrinology in Breast Cancer and Diabetes (Northwell Health)

Postdoctoral Fellow – T-Cell Immunotherapy in Cancers (Memorial Sloan Kettering Cancer Center)

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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