Mammary Cell News Volume 7.14 | Apr 16 2015

Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast Cancer by Targeting BET Family Bromodomains
Genetic and chemical inhibition of BET bromodomain chromatin readers suppresses transcription of many lapatinib-induced kinases involved in resistance, including ERBB3, IGF1R, DDR1, MET, and FGFRs, preventing downstream SRC/FAK signaling and AKT reactivation. [Cell Rep]
Full Article | Graphical Abstract | Press Release

Targeting Matriptase in Breast Cancer Abrogates Tumor Progression via Impairment of Stromal-Epithelial Growth Factor Signaling
Researchers demonstrated by genetic deletion and silencing that the proliferation impairment in matriptase-deficient breast cancer cells is caused by their inability to initiate activation of the c-Met signaling pathway in response to fibroblast-secreted pro-HGF. [Nat Commun] Abstract

Silencing β3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple Negative Breast Cancer
Scientists exploited β3 integrin as a therapeutic target to treat triple-negative breast cancer (TNBC) by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/siβ3). Treatment of TNBC cells with ECO/siβ3 was sufficient to effectively silence β3 integrin expression, attenuate TGF-β-mediated epithelial-mesenchymal transition and invasion, restore TGF-β-mediated cytostasis, and inhibit 3-dimensional organoid growth. [Cancer Res] Abstract | Full Article

MiRNA-621 Sensitizes Breast Cancer to Chemotherapy by Suppressing FBXO11 and Enhancing p53 Activity
Ectopic overexpression of miR-621 promoted apoptosis and increased chemosensitivity to paclitaxel and carboplatin both in cultured breast cancer cells and in xenograft tumor model. [Oncogene] Full Article

Oroxylin A Inhibits Glycolysis-Dependent Proliferation of Human Breast Cancer via Promoting SIRT3-Mediated SOD2 Transcription and HIF1α Destabilization
Investigators showed that oroxylin A inhibited glycolysis in breast cancer cells via the sirtuin 3 (SIRT3)-mediated destabilization of hypoxia-inducible factor 1α (HIF1α), which controls glycolytic gene expression. Oroxylin A promoted superoxide dismutase (SOD2) gene expression through SIRT3-regulated DNA-binding activity of FOXO3a and increased the activity of SOD2 by promoting SIRT3-mediated deacetylation. [Cell Death Dis] Full Article

HIF-Inducible miR-191 Promotes Migration in Breast Cancer through Complex Regulation of TGFβ-Signaling in Hypoxic Microenvironment
Hypoxia through hypoxia-inducible factor (HIF) brought about a time-dependent increase in the level of an oncogenic microRNA, miR-191 in various breast cancer cell lines. miR-191 enhanced breast cancer aggressiveness by promoting cell proliferation, migration and survival under hypoxia. [Sci Rep] Full Article

CRLX101, an Investigational Camptothecin-Containing Nanoparticle-Drug Conjugate, Targets Cancer Stem Cells and Impedes Resistance to Antiangiogenic Therapy in Mouse Models of Breast Cancer
Researchers tested whether inhibiting hypoxia-inducible factor 1α (HIF-1α) can reverse the stimulatory effects of antiangiogenic-induced hypoxia on breast cancer stem cells (CSCs). Breast cancer cells grown under hypoxic conditions were treated with the dual topoisomerase-1 and HIF-1α inhibitor camptothecin and assessed for their CSC content. [Breast Cancer Res Treat] Abstract | Press Release

Oxidative Stress Shapes Breast Cancer Phenotype through Chronic Activation of ATM-Dependent Signaling
Researchers showed that, in MDA-MB-231 and HeLa cells, basal ATM-dependent NF-κB activation occurs through a canonical DNA damage-responsive signaling pathway as knockdown of two proteins involved in this signaling pathway, ERC1 and TAB1, results in loss of NF-κB basal activity. [Breast Cancer Res Treat] Abstract

The Active Tamoxifen Metabolite Endoxifen (4OHNDtam) Strongly Down-Regulates Cytokeratin 6 (CK6) in MCF-7 Breast Cancer Cells
The authors investigated the gene regulatory effects of the three metabolites of tamoxifen in MCF-7 breast cancer cells. Using concentrations that mimic the clinical situation, they examined effects of 4-hydroxytamoxifen, 4OHNDtam and ndesmethyltamoxifen on global gene expression in 17β-estradiol treated MCF-7 cells. [PLoS One] Abstract

CLINICAL RESEARCH

Phase II Study of Gemcitabine, Carboplatin, and Iniparib as Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer with Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105
Scientists assessed efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer. [J Clin Oncol] Abstract

Randomized Study of Orally Administered Fluorinated Pyrimidines (Capecitabine versus S-1) in Women with Metastatic or Recurrent Breast Cancer: Japan Breast Cancer Research Network 05 Trial
Capecitabine and S-1 are orally administered fluorinated pyrimidines with high-level activity against metastatic breast cancer. This randomized, multicenter, Phase II study compared the activities and safeties of the oral fluoropyrimidines, capecitabine and S-1, in breast cancer patients. [Cancer Chemother Pharmacol] Abstract

Medivir and Cancer Research Technology Collaborate to Develop New Class of Cancer Drugs
Medivir AB and Cancer Research Technology, Cancer Research UK’s commercialization and development arm, jointly announced a partnership to develop a new class of drugs that has shown promise for treating a range of different cancers. [Medivir AB] Press Release

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