LABORATORY RESEARCH ID4 Controls Mammary Stem Cells and Marks Breast Cancers with a Stem Cell-Like Phenotype Investigators showed that ​inhibitor of differentiation 4 (​ID4) is a key regulator of mammary stem cell self-renewal and marks a subset of basal-like breast cancer with a putative mammary basal cell of origin. [Nat Commun] Abstract | Press Release ​Skp2-MacroH2A1-CDK8 Axis Orchestrates G2/M Transition and Tumorigenesis Researchers report that breast tumor suppression on ​Skp2 deficiency can be rescued by ​macroH2A1 (​mH2A1) knockdown or ​cyclin-dependent kinase 8 (​CDK8) restoration using mouse tumor models. They further showed that ​CDK8 regulated p27 protein expression by facilitating ​Skp2-mediated ​p27 ubiquitination and degradation. [Nat Commun] Full Article Manic Fringe Promotes a Claudin-Low Breast Cancer Phenotype through Notch-Mediated PIK3CG Induction Researchers showed that Manic Fringe (Mfng) modulates Notch activation in human and mouse claudin-low breast cancer (CLBC) cell lines, as well as in mouse mammary gland. Mfng silencing in CLBC cell lines reduced cell migration, tumorsphere formation and in vivo tumorigenicity associated with a decrease in the stem-like cell population. [Cancer Res] Abstract Fibulin-3 Is a Novel TGF-β Pathway Inhibitor in the Breast Cancer Microenvironment Researchers identified fibulin-3 as a secreted protein in the breast cancer microenvironment, which efficiently inhibits transforming growth factor-β (TGF-β) signaling in both breast cancer cells and endothelial cells. High fibulin-3 levels inhibited TGF-β-induced epithelial-mesenchymal transition, migration, invasion and endothelial permeability, while loss of fibulin-3 expression/function promoted these TGF-β-mediated effects. [Oncogene] Abstract Blocking the Adhesion Cascade at the Pre-Metastatic Niche for Prevention of Breast Cancer Metastasis Investigators found that the vascular adhesion molecule E-selectin preferentially promoted the shear-resistant adhesion and transendothelial migration of estrogen receptor (ER)-negative/CD44+ hormone-independent breast cancer cells, but not of ER-positive/CD44–/low hormone-dependent cancer cells. [Mol Ther] Abstract FAK Activity Protects Nucleostemin in Facilitating Breast Cancer Spheroid and Tumor Growth Human breast carcinoma cells were evaluated for growth in culture and as orthotopic tumors. Researchers found that pharmacological or genetic inhibition of focal adhesion kinase (FAK) activity prevented MDA-MB-231 and 4T1L breast carcinoma growth as spheroids and as orthotopic tumors. [Breast Cancer Res] Abstract | Full Article YAP Enhances Autophagic Flux to Promote Breast Cancer Cell Survival in Response to Nutrient Deprivation Researchers investigated the role of Yes-associated protein (YAP) in breast cancer cells under nutrient deprivation. They showed that YAP knockdown sensitized MCF7 breast cancer cells to nutrient deprivation-induced apoptosis. [PLoS One] Full Article Stanniocalicin 2 Suppresses Breast Cancer Cell Migration and Invasion via the PKC/Claudin-1-Mediated Signaling The authors investigated whether the expression of stanniocalcin (STC) 2 is associated with migration and invasion of breast cancer cells. They found that breast cancer cell line 231 HM transfected with STC2 shRNA displayed high motility, fibroblast morphology, and enhanced cell migration and invasion. [PLoS One] Full Article CLINICAL RESEARCH Loss of TGFβ Receptor Type 2 Expression Impairs Estrogen Response and Confers Tamoxifen Resistance Scientists analyzed TGFβ receptor type 2 (TGFBR2) expression and correlated it with estrogen receptor α status and phosphorylation in a cohort of 564 patients who had been randomized to tamoxifen or no-adjuvant treatment for invasive breast carcinoma. In all the cohorts they analyzed, they documented an association of low TGFBR2 protein and mRNA expression with tamoxifen resistance. [Cancer Res] Abstract | Press Release A Phase I Clinical Trial of Bavituximab and Paclitaxel in Patients with HER2 Negative Metastatic Breast Cancer Investigators conducted a Phase I clinical trial of bavituximab in combination with paclitaxel in patients with HER2-negative metastatic breast cancer. [Cancer Medicine] Full Article |