Mammary Cell News Volume 11.00 | Jan 10 2019

TOP STORY

Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling

Researchers showed that ectopic expression and therapeutic delivery of the secreted protein tubulointerstitial nephritis antigen-like 1 (Tinagl1) suppressed triple-negative breast cancer progression and metastasis through direct binding to integrin α5β1, αvβ1, and epidermal growth factor receptor (EGFR), and subsequent simultaneous inhibition of focal adhesion kinase (FAK) and EGFR signaling pathways. [Cancer Cell] Abstract | Graphical Abstract

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BRCA2 Deficiency Instigates cGAS-Mediated Inflammatory Signaling and Confers Sensitivity to Tumor Necrosis Factor-Alpha-Mediated Cytotoxicity

BRCA2 inactivation led to pro-inflammatory cytokine production, including tumor necrosis factor-alpha (TNFα), and increased sensitivity to TNFα. Enhanced TNFα sensitivity was not restricted to BRCA2 inactivation, as BRCA1 or FANCD2 inactivation, or hydroxyurea treatment also sensitized cells to TNFα. [Nat Commun] Full Article

Inhibition of Chemotherapy Resistant Breast Cancer Stem Cells by a ROR1 Specific Antibody

Scientists found that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog. [Proc Natl Acad Sci USA] Full Article

WWOX Inhibits Metastasis of Triple-Negative Breast Cancer Cells via Modulation of MicroRNAs

Investigators reported that WWOX inactivation correlated with advanced stages of triple-negative breast cancer (TNBC) and that its levels were frequently altered in TNBC cells. Ectopic restoration of WWOX in WWOX-negative TNBC cells inhibited metastasis while its depletion in WWOX-positive TNBC cells promoted metastasis. [Cancer Res] Abstract

Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells

Scientists demonstrated that LYN was a downstream effector of c-KIT in normal mammary cells and protective of apoptosis upon genotoxic stress. LYN activity was modulated by PIN1, a prolyl isomerase, and in BRCA1 mutant triple-negative/basal-like breast cancer PIN1 upregulation activated LYN independently of c-KIT. [Cell Rep] Full Article | Graphical Abstract

The circRNA circAGFG1 Acts as a Sponge of miR-195-5p to Promote Triple-Negative Breast Cancer Progression through Regulating CCNE1 Expression

Researchers found that circAGFG1 was evidently up-regulated in triple-negative breast cancer (TNBC), and its level was correlated with clinical stage, pathological grade and poor prognosis of patients with TNBC. [Mol Cancer] Full Article

Activation of lncRNA TINCR by H3K27 Acetylation Promotes Trastuzumab Resistance and Epithelial-Mesenchymal Transition by Targeting MicroRNA-125b in Breast Cancer

The expression level of terminal differentiation-induced non-coding RNA (TINCR) was significantly increased in trastuzumab-resistant cells when compared with sensitive cells. Knockdown of TINCR reversed the trastuzumab resistance and the acquired epithelial-mesenchymal transition in these cells. [Mol Cancer] Full Article

FYN Promotes Mesenchymal Phenotypes of Basal Type Breast Cancer Cells through STAT5/NOTCH2 Signaling Node

FYN enhanced NOTCH2 activation in basal type breast cancer cells through STAT5-mediated upregulation of Jagged-1 and DLL4 NOTCH ligands, and thereby contributed to mesenchymal phenotypes. [Oncogene] Abstract

Interactions between Cancer-Associated Fibroblasts and Tumor Cells Promote MCL-1 Dependency in Estrogen Receptor-Positive Breast Cancers

Scientists showed that the BCL-2 dependency of luminal tumor cells was mitigated by breast cancer-associated fibroblasts (bCAFs) in a manner that defined MCL-1 as another critical therapeutic target. bCAFs favored MCL-1 expression and apoptotic resistance in luminal cancer cells in a IL-6 dependent manner while their own, robust, survival also relied on MCL-1. [Oncogene] Full Article

Upregulated Osterix Promotes Invasion and Bone Metastasis and Predicts for a Poor Prognosis in Breast Cancer

Knockdown of osterix (Osx) inhibited the invasion of breast cancer and osteolytic metastasis by downregulating MMP9, MMP13, VEGF, IL-8, and PTHrP, which were involved in invasion, angiogenesis, and osteolysis; overexpression of Osx had the opposite effect. [Cell Death Dis] Full Article

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RANKL/RANK/OPG System beyond Bone Remodeling: Involvement in Breast Cancer and Clinical Perspectives

The authors focus on molecular mechanisms linking receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/receptor activator of NF-kB (RANK)/osteoprotegerin (OPG) system to mammary tumorigenesis, highlighting pre-clinical and clinical evidence for the potential efficacy of RANKL inhibition as a prevention strategy and adjuvant therapy in breast cancer settings. [J Exp Clin Cancer Res] Full Article

LncRNA Differential Expression in Breast Cancer Subtypes: What Do We Know?

Investigators focus on long non-coding RNAs (lncRNAs) with differential expression in breast cancer (BC) subtypes and how these RNAs may act to contribute to BC heterogeneity. They also emphasize the potential of these lncRNAs as biomarkers. [Clin Genet] Abstract

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Athenex Announces Completion of Target Enrollment in the Oraxol Phase III Study

Athenex, Inc. announced that target enrollment of 360 patients in the Oraxol Phase III clinical trial in metastatic breast cancer has been achieved on schedule. Athenex also reaffirmed that top line data from the study is expected to be available in mid-2019. [Athenex, Inc.] Press Release

Evelo Biosciences Announces Dosing of First Patient in Phase I/II Clinical Trial of EDP1503 in Combination with KEYTRUDA^® (Pembrolizumab) in Multiple Oncology Indications

This open-label clinical trial will evaluate the safety, tolerability, immune response markers, and overall response rates achieved with EDP1503 in combination with KEYTRUDA^® in up to 120 patients across three groups: microsatellite stable colorectal cancer; triple-negative breast cancer; and patients across multiple tumor types who have relapsed on prior PD-1/L1 inhibitor treatment. [Evelo Biosciences, Inc.] Press Release

Hemispherx Biopharma Announces IRB Approval of Clinical Study in Metastatic Triple Negative Breast Cancer in Collaboration with Roswell Park Comprehensive Cancer Center

Hemispherx Biopharma, Inc. announced Roswell Park Comprehensive Cancer Center Institutional Review Board (IRB) approval and shipment of Ampligen to start an oncology clinical study combining its dsRNA TLR3 agonist Ampligen with Merck’s pembrolizumab in metastatic triple negative breast cancer. [Hemispherx Biopharma, Inc.] Press Release

Generex Biotechnology Provides Update on NuGenerex Immuno-Oncology

The protocol for the Phase II clinical trial of pembrolizumab in combination with the AE37 peptide vaccine in patients with metastatic triple negative breast cancer is under review at the Institutional Review Board with oversight of this NSABP Foundation managed study. [Generex Biotechnology Corporation] Press Release

Indian Scientists Protest against Unscientific Claims Made at Conference

Indian scientists have criticized two speakers at a major conference for making bizarre, unscientific claims, including that ancient Hindus invented stem-cell science. Groups of researchers held protests in Bangalore, Kochi, Kolkata and Thiruvananthapuram on 6 January, calling for an end to presentations at the Indian Science Congress that promote unscientific personal beliefs. [Nature News] Editorial

Colombia Creates Its First Science Ministry

Colombian scientists are cautiously optimistic after the country’s Senate voted to create the nation’s first Ministry of Science, Technology and Innovation. [Nature News] Editorial

Taiwanese Biochemist Cleared of Corruption

A Taiwanese court has cleared biochemist Wong Chi-huey of corruption. Wong, a former head of Taiwan’s foremost research institution, Academia Sinica, had been accused of accepting shares as a bribe for helping the Taiwanese biopharmaceutical firm OBI Pharma secure the rights to use enzyme-synthesis technology that he had developed. Wong denies he did anything illegal. [Nature News] Editorial

NEW Keystone Symposia: Cancer Stem Cells – Advances in Biology & Clinical Translation
October 13-17, 2019
Hong Kong, China

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NEW Postdoctoral Fellow – Breast Cancer Research (City of Hope)

NEW Faculty Position – Molecular Cancer Biology (University of Pittsburgh)

NEW Faculty Position – Breast Cancer (University of Texas MD Anderson Cancer Center)

Postdoctoral Associate – Cancer (University of Miami)

Postdoctoral Position – Breast Cancer (Northwestern University)

Research Associate – Breast Single Cell Atlas (University of Cambridge)

Research Assistant – Breast Medical Oncology (MD Anderson Cancer Center)

Associate Researcher – Breast Cancer Biology (Icahn School of Medicine at Mount Sinai)

Research Fellow – Breast Cancer (International Iberian Nanotechnology Laboratory)

Master’s Student – Stem Cell Biology and Cancer (Helmholtz-Center München)

Faculty Position – Cancer Cell Signaling (The University of New Mexico Comprehensive Cancer Center)

Postdoctoral Position – Novel Cancer Gene and Therapy (University of Notre Dame)

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