Mammary Cell News Volume 11.44 | Nov 14 2019

TOP STORY

Double PIK3CA Mutations in Cis Increase Oncogenicity and Sensitivity to PI3Kα Inhibitors

Investigators analyzed PIK3CA-mutant cancer genomes and observed the presence of multiple PIK3CA mutations in 12 to 15% of breast cancers and other tumor types, most of which (95%) were double mutations. [Science] Abstract

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CDK2-Mediated Site-Specific Phosphorylation of EZH2 Drives and Maintains Triple-Negative Breast Cancer

Scientists showed that transgenic expression of phospho-mimicking EZH2 mutant EZH2T416D in mammary glands led to tumors with triple-negative breast cancer (TNBC) phenotype. Pharmacological inhibition of CDK2 or EZH2 allowed re-expression of ERα and converted TNBC to luminal ERα-positive, rendering TNBC cells targetable by tamoxifen. [Nat Commun] Full Article

Reduced RhoA Expression Enhances Breast Cancer Metastasis with a Concomitant Increase in CCR5 and CXCR4 Chemokines Signaling

Using a syngeneic triple negative breast cancer murine model, researchers investigated the physiological effects of reduced RhoA expression on breast cancer tumorigenesis and metastasis. [Nat Commun] Full Article

Differential Contributions of Pre- and Post- EMT Tumor Cells in Breast Cancer Metastasis

The authors evaluated Tri-PyMT cells at the single-cell level using single-cell RNA-sequencing, and found that the Tri-PyMT cells exhibited a spectrum of epithelial-to-mesenchymal transition (EMT) phenotypes, with EMT-related genes concomitantly expressed with the activation of GFP. [Cancer Res] Abstract

A Luminescent Amine-Functionalized Metal-Organic Framework Conjugated with Folic Acid as a Targeted Biocompatible pH-Responsive Nanocarrier for Apoptosis Induction in Breast Cancer Cells

Folic acid amine-functionalized metal-organic framework with luminescent properties loaded with 5-fluorouracil, as an anticancer medication, was used to construct a new cancer targeted drug delivery system. [ACS Appl Mater Interfaces] Abstract

CAIX Forms a Transport Metabolon with Monocarboxylate Transporters in Human Breast Cancer Cells

Investigators demonstrated that carbonic anhydrase IX (CAIX), one of the major acid/base regulators in cancer cells, formed a protein complex with monocarboxylate transporter 1 (MCT1) and MCT4 in tissue samples from human breast cancer patients, but not healthy breast tissue. [Oncogene] Abstract

Paget’s Disease of the Nipple in a Her2-Positive Breast Cancer Xenograft Model

HER2-enriched DT13 breast cancer cells were injected into the mammary fat pad of NOD scid gamma null female mice. In addition, DT13 cells grown in 2D culture and in soft agar assays were sensitive to in vitro treatment with pharmacological inhibitors targeting Her2, adenylyl cyclase, mTOR, and PI3K signaling pathways. [Breast Cancer Res Treat] Abstract

Acetylation of Conserved DVL-1 Lysines Regulates Its Nuclear Translocation and Binding to Gene Promoters in Triple-Negative Breast Cancer

The authors reported 12 dishevelled-1 (DVL-1) lysine residues that showed differential acetylation in response to changes in oxygen tension and deacetylase inhibition in triple-negative breast cancer. [Sci Rep] Full Article

Cell Proliferation and Invasion Are Regulated Differently by EGFR and MRP1 in T-DM1-Resistant Breast Cancer Cells

Scientists showed that EGFR positively coordinated with MRP1 in T-DM1R-JIMT1 cells to contribute to cross-resistance to doxorubicin. Downregulating EGFR and MRP1 inhibited T-DM1R-JIMT1 cell growth and re-sensitized T-DM1R cells to doxorubicin. [Sci Rep] Full Article

STEAP2 Is Down-Regulated in Breast Cancer Tissue and Suppresses PI3K/AKT Signaling and Breast Cancer Cell Invasion In Vitro and In Vivo.

STEAP2 mRNA and protein expressions in breast normal and cancer tissues, breast cancer cell lines and normal mammary epithelial cell lines were evaluated by immunohistochemistry, real time RT-qPCR and western blotting. [Cancer Biol Ther] Abstract

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The Aryl Hydrocarbon Receptor (AhR) as a Breast Cancer Drug Target

The authors examine the current state of the literature in this area and elucidate the promising advances that are being made in hijacking the cytosolic-to-nuclear pathway of the aryl hydrocarbon receptor for the possible future treatment of breast cancer. [Med Res Rev] Abstract

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CytoDyn Receives IRB Approval to Proceed with Compassionate Use of Leronlimab for Patients with Triple-Negative Breast Cancer

CytoDyn Inc. announced it has received approval from the Institutional Review Board (IRB) for leronlimab to be administered to patients with triple-negative breast cancer under a compassionate use, which is also known as expanded access program. [CytoDyn Inc] Press Release

Translational Research in Oncology (TRIO) Initiates Phase I Study for MT-5111

Translational Research in Oncology (TRIO) announced enrolment of the first patient in a Phase I study with its partner Molecular Templates. [TRIO (Translational Research In Oncology)] Press Release

Italy to Launch National Agency for Research

Just two months after Italy underwent a crisis of government and established an alliance between two leading political parties, the left-of-center Democratic Party and the anti-establishment Five Star Movement, the country has announced plans to start a National Agency for Research to help oversee the distribution of federal funds. [The Scientist] Editorial

EPA’s ‘Secret Science’ Plan Is Back, and Critics Say It’s Worse

Critics are blasting a revised Trump administration plan to give the US Environmental Protection Agency (EPA) broad power to ignore research results when setting public health rules if officials decide the underlying data are not adequately accessible to the public. [ScienceInsider] Editorial

The Mental Health of PhD Researchers Demands Urgent Attention

Two years ago, a student responding to Nature’s biennial PhD survey called on universities to provide a quiet room for “crying time” when the pressures caused by graduate study become overwhelming. At that time, 29% of 5,700 respondents listed their mental health as an area of concern – and just under half of those had sought help for anxiety or depression caused by their PhD study. Things seem to be getting worse. [Nature News] Editorial

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NEW Postdoctoral Studentship – Focal Adhesions in Metastatic Breast Cancer (German Cancer Research Center in the Helmholtz Association)

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Postdoctoral Fellow – Breast Cancer Stem Cells (Dalhousie University)

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

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