LABORATORY RESEARCH The Cell Cycle Regulator 14-3-3σ Opposes and Reverses Cancer Metabolic Reprogramming Investigators showed that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3σ opposed tumor-promoting metabolic programs by enhancing c-Myc poly-ubiquitination and subsequent degradation. [Nat Commun] Abstract | Press Release DNA Methylation of Estrogen-Regulated Enhancers Defines Endocrine Sensitivity in Breast Cancer Researchers showed that DNA hypermethylation occurs predominantly at estrogen-responsive enhancers and is associated with reduced expression of estrogen receptor (ESR1) binding and decreased gene expression of key regulators of ESR1 activity, thus providing a novel mechanism by which endocrine response is abated in ESR1-positive breast cancers. [Nat Commun] Full Article Dysregulated Protease Activated Receptor 1 (PAR1) Promotes Metastatic Phenotype in Breast Cancer through HMGA2 PAR1 expression increased spheroid formation and the level of stemness markers and self-renewal capacity in human breast cancer cells. [Oncogene] Abstract Acquisition of Estrogen Independence Induces TOB1-Related Mechanisms Supporting Breast Cancer Cell Proliferation Depletion of TOB1 selectively promoted G1 phase arrest and sensitivity to AKT and mammalian target of rapamycin inhibitors in estrogen-independent cells but not in estrogen-dependent cells. [Oncogene] Abstract Wild-Type N-Ras, Overexpressed in Basal-Like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation Researchers identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. [Cell Rep] Full Article | Graphical Abstract | Press Release Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation Fe65 is a brain-enriched adaptor protein known for its role in the action of the Aβ amyloid precursor protein in neuronal cells and Alzheimer’s disease, but little is known about its functions in cancer cells. The authors present a role of Fe65 in suppressing breast cancer cell migration and invasion. [Sci Rep] Full Article Analysis of Gene Expression of Secreted Factors Associated with Breast Cancer Metastases in Breast Cancer Subtypes The authors characterized the relative gene expression of the five secreted molecules and their associated receptors in the basal, human epidermal growth factor receptor 2 positive, luminal A, and luminal B subtypes using high throughput data from tumor samples in The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium. [Sci Rep] Full Article Estrogen Receptor α Regulates Non-Canonical Autophagy that Provides Stress Resistance to Neuroblastoma and Breast Cancer Cells and Involves BAG3 Function Researchers characterized tumor cell lines ectopically expressing estrogen recepter (ER)α or ERβ as well as the breast cancer-derived MCF-7 cell line endogenously expressing ERα but being ERβ negative. They showed that ERα-expressing cells have a higher autophagic activity than cells expressing ERβ and cells lacking ER expression. [Cell Death Dis] Full Article LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer Cells Scientists identified heterogeneous nuclear ribonucleoprotein A1, a protein with multiple roles in mRNA metabolism, as a LIN28 interacting partner. Results reveal these proteins regulate alternative splicing and steady state mRNA expression of genes implicated in aspects of breast cancer biology. [Mol Cell Biol] Abstract CLINICAL RESEARCH Phase II Study of Lapatinib in Combination with Trastuzumab in Patients with Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging Lapatinib plus trastuzumab improves outcomes relative to lapatinib alone in heavily pretreated, human epidermal growth factor receptor 2–positive metastatic breast cancer. Researchers tested the combination in the earlier-line setting and explored the predictive value of [18F]fluorodeoxyglucose positron emission tomography for clinical outcomes. [J Clin Oncol] Abstract Phase I/II Trial of Neoadjuvant Sunitinib Administered with Weekly Paclitaxel/Carboplatin in Patients with Locally Advanced Triple-Negative Breast Cancer Investigators evaluated the feasibility and efficacy of adding sunitinib to paclitaxel/carboplatin in the neoadjuvant therapy of patients with triple-negative breast cancer. [Breast Cancer Res Treat] Abstract |