Impact of Deleterious Passenger Mutations on Cancer Progression Cancer progression is driven by the accumulation of a small number of genetic alterations. However, these few driver alterations reside in a cancer genome alongside tens of thousands of additional mutations termed passengers. Researchers investigated the potential of moderately deleterious passengers to accumulate and alter the course of neoplastic progression. The results suggest a unique framework for understanding cancer progression as a balance of driver and passenger mutations. [Proc Natl Acad Sci USA] Abstract | Press Release Direct Reprogramming by Oncogenic Ras and Myc Scientists used a model of conditional expression of oncogenic KrasG12D allele in primary mouse cells to show that reprogramming and dedifferentiation is a fundamental early step in malignant transformation and cancer initiation. [Proc Natl Acad Sci USA] Abstract CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer Findings revealed the function of cellular prion protein (PrPc) in regulating epithelial to mesenchymal transition in cancer stem cells, and identified PrPc as candidate therapeutic target in metastatic colorectal cancer. [Cancer Res] Abstract | Full Article Differential Contributions of STAT5A and STAT5B to Stress Protection and Tyrosine Kinase Inhibitor Resistance of Chronic Myeloid Leukemia Stem/Progenitor Cells Findings demonstrated that STAT5A has a selective role in contributing to stress resistance through unconventional mechanisms, offering new opportunities to eradicate the most primitive and TKI- resistant chronic myeloid leukemia cells with an additional potential to eradicate persistent stem cell populations. [Cancer Res] Abstract Targeting the Cytosolic Innate Immune Receptors RIG-I and MDA5 Effectively Counteracts Cancer Cell Heterogeneity in Glioblastoma Cellular heterogeneity, e.g., the intratumoral coexistence of cancer cells with and without stem cell characteristics, represents a potential root of therapeutic resistance and a significant challenge for modern drug development in glioblastoma. Researchers proposed that activation of the innate immune system by stimulation of innate immune receptors involved in antiviral and antitumor responses can similarly target different malignant populations of glioma cells. [Stem Cells] Abstract Mesenchymal Stromal Cell Atrophy in Co-Culture Increases Aggressiveness of Transformed Cells Researchers showed that papillary thyroid cancer TPC1 and HEK 293T cells interact physically with human primary bone marrow-derived mesenchymal stromal cells (MSCs) followed by evanescence of MSC cytoplasm. The co-culture model system describes how adjacent transformed cells absorb stromal cells thereby leading to the stroma-driven evolution of moderately carcinogenic cells to highly aggressive metastatic cells. [Stem Cells] Abstract Synthesis and Cancer Stem Cell-Based Activity of Substituted 5-Morpholino-7H-thieno[3,2-b]pyran-7-ones Designed as Next Generation PI3K Inhibitors This work resulted in the discovery of the 5-morpholino-7H-thieno[3,2-b]pyran-7-one system as the foundation of a new compound class of potential phosphatidylinositol-3-kinase (PI3K) inhibitors having improved potency towards PI3K. The synthesis and cancer stem cell-based activity of these compounds are reported. [J Med Chem] Abstract Krüppel-Like Factor 4 Acts as an Oncogene in Colon Cancer Stem Cell-Enriched Spheroid Cells Investigators found that culturing DLD-1 cells, one type of cells derived from colon cancers, in serum-free medium enriches cancer stem cells (CSCs) and the expression of Krüppel-like factor 4 (KLF4) is essential for the characteristics of CSCs in DLD-1. [PLoS One] Full Article  |