LABORATORY RESEARCH ANTXR1, A Stem Cell Enriched Functional Biomarker, Connects Collagen Signaling to Cancer Stem-Like Cells and Metastasis in Breast Cancer The anthrax toxin receptor ANTXR1 has been identified as a functional biomarker of normal stem cells and breast cancer stem-like cells. Primary stem cell-enriched basal cells (CD49f+/EpCAM-/Lin-) expressed higher levels of ANTXR1 compared to mature luminal cells. CD49f+/EpCAM-, CD44+/EpCAM-, CD44+/CD24- or ALDEFLUOR-positive subpopulations of breast cancer cells were enriched for ANTXR1 expression. [Cancer Res] Abstract Distinct FAK Activities Determine Progenitor and Mammary Stem Cell Characteristics Researchers showed that conditional deletion of focal adhesion kinase (FAK) in embryonic mammary epithelial cells decreases luminal progenitors and basal mammary stem cells, reducing their colony-forming and regenerative potentials in a cell autonomous manner. [Cancer Res] Abstract Insulin Receptor Phosphorylation by Endogenous Insulin or the Insulin Analog AspB10 Promotes Mammary Tumor Growth Independent of the IGF-1 Receptor Scientists hypothesized that endogenous hyperinsulinemia increases mammary tumor growth by directly activating the insulin receptor (IR) rather than the insulin-like growth factor-1 receptor (IGF-1R) or hybrid receptors. They aimed to determine whether stimulating the IR with the insulin analog AspB10 could increase tumor growth independent of IGF-1R signaling. [Diabetes] Abstract Regulation of Cell Proliferation and Migration by Keratin19-Induced Nuclear Import of Early Growth Response-1 in Breast Cancer Cells The authors investigated the functional analysis of keratin19 (KRT19) in human breast cancer. Using a shRNA system, they silenced KRT19 in breast cancer cells. KRT19 silencing was verified by western blot analysis and immunocytochemistry. They further examined the effect of KRT19 silencing on breast cancer cells by cell proliferation, migration, invasion, colony formation assay, cell cycle analysis, immunocytochemistry, immunohistochemistry and mouse xenograft assay. [Clin Cancer Res] Abstract MicroRNA-19a-3p Inhibits Breast Cancer Progression and Metastasis by Inducing Macrophage Polarization through Downregulated Expression of Fra-1 Proto-Oncogene Investigators demonstrated that microRNA-19a-3p, broadly conserved among vertebrates, was downregulated in RAW264.7 macrophage cells of the M2 phenotype in conditoned medium of 4T1 mouse breast tumor cells. This downregulation correlated with an increased expression of the Fra-1 gene, which was reported to act as a pro-oncogene by supporting the invasion and progression of breast tumors. [Oncogene] Abstract Identification of p130Cas/ErbB2-Dependent Invasive Signatures in Transformed Mammary Epithelial Cells By comparing coding and non-coding gene expression profiles, the authors defined the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. [Cell Cycle] Abstract Bone Morphogenetic Proteins Stimulate Mammary Fibroblasts to Promote Mammary Carcinoma Cell Invasion Researchers sought to determine the effect of Bone Morphogenetic Protein (BMP) treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases were found to be upregulated in response to BMP4 treatment. [PLoS One] Full Article Mitochondrial Bioenergetics of Metastatic Breast Cancer Cells in Response to Dynamic Changes in Oxygen Tension: Effects of HIF-1α A novel experimental approach was developed to examine the real-time bioenergetic changes in breast cancer cells (BCCs) during adaptation to oxygen tension using sensitive extracellular flux technology. Oxygen was gradually removed from the medium, and the bioenergetics of metastatic BCCs was compared with non-tumorigenic cells. [PLoS One] Full Article CLINICAL RESEARCH Trastuzumab Emtansine in the Treatment of HER-2-Positive Metastatic Breast Cancer Patients Trastuzumab emtansine is a HER-2-targeted antibody-drug conjugate, composed of the cytotoxic microtubule polymerization inhibitor DM1 that is conjugated to the monoclonal antibody trastuzumab, able to selectively deliver a cytotoxic agent to HER-2-positive tumor cells. TDM-1 is superior and less toxic than lapatinib plus capecitabine in metastatic breast cancer patients previously treated with trastuzumab and taxanes, and its role as a first-line therapy is currently under investigation. [Future Oncol] Abstract Clinicopathological Features Among Patients with Advanced Human Epidermal Growth Factor-2-Positive Breast Cancer with Prolonged Clinical Benefit to First-Line Trastuzumab-Based Therapy: A Retrospective Cohort Study Scientists investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. [Clin Breast Cancer] Abstract |