New IDH1 Mutant Inhibitors for Treatment of Acute Myeloid Leukemia Investigators report the development of new allosteric inhibitors of mutant IDH1. Treatment of IDH1 mutant primary acute myeloid leukemia cells uniformly led to a decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells, in vitro and in vivo. [Nat Chem Biol] Abstract Model of Fibrolamellar Hepatocellular Carcinomas Reveals Striking Enrichment in Cancer Stem Cells The authors present a transplantable tumor line, maintained in immune-compromised mice, and validate it as a bona fide model of human fibrolamellar hepatocellular carcinomas (hFL-HCCs) by multiple methods. The hFL-HCC tumor line is highly enriched for cancer stem cells as indicated by limited dilution tumorigenicity assays, spheroid formation and flow cytometry. [Nat Commun] Full Article An LSC Epigenetic Signature Is Largely Mutation Independent and Implicates the HOXA Cluster in AML Pathogenesis Scientists showed a leukemia stem cell DNA methylation signature, derived from xenografts and integration with gene expression that is comprised of 71 genes and identified a key role for the HOXA cluster. [Nat Commun] Full Article An Imbalance in TAZ and YAP Expression in Hepatocellular Carcinoma Confers Cancer Stem Cell-Like Behaviors Contributing to Disease Progression Researchers examined the functional roles of transcriptional co-activator with PDZ-binding motif (TAZ)/yes-associated protein (YAP) in hepatocellular carcinoma (HCC) progression. Notably, TAZ knockdown induced compensatory YAP expression and was accompanied by upregulation of CD90, a HCC-specific cancer stem cell marker. [Cancer Res] Abstract Mitochondrial Mass, a New Metabolic Biomarker for Stem-Like Cancer Cells: Understanding WNT/FGF-Driven Anabolic Signaling Researchers developed an isogenic cell model of “stemness” to facilitate protein biomarker discovery in breast cancer. Mouse mammary tumor virus initiated mammary tumorigenesis in mice by promoter insertion adjacent to two main integration sites, namely Int-1 and Int-2, which ultimately activated Wnt/β-catenin signaling, driving the propagation of mammary cancer stem cells. [Oncotarget] Full Article High Mitochondrial Mass Identifies a Sub-Population of Stem-Like Cancer Cells that Are Chemo-Resistant Investigators used breast cell lines and metastatic breast cancer patient samples to begin to dissect the role of mitochondrial metabolism in conferring the cancer stem-like cell phenotype. [Oncotarget] Full Article HIF2α Is Involved in the Expansion of CXCR4-Positive Cancer Stem-Like Cells in Renal Cell Carcinoma Scientists suggest that the generation of renal cell carcinoma (RCC)-derived CSCs involves the activation of hypoxia-inducible factor-2α (HIF2α) and may provide a foundation for the development of new strategies to prevent the induction of CSCs in RCC. [Br J Cancer] Abstract P-Cadherin and the Journey to Cancer Metastasis Investigators studied P-cadherin signaling pathways that are activated to induce invasion and metastasis, as well as cancer stem cell properties. The signaling network downstream of P-cadherin is notably dependent on the cellular and tissue context and includes the activation of integrin molecules, receptor tyrosine kinases, small molecule GTPases, EMT transcription factors, and crosstalk with other cadherin family members. [Mol Cancer] Full Article New Ex-Ovo Colorectal-Cancer Models from Different SdFFF-Sorted Tumor-Initiating Cells On the basis of a new strategy, including tumor-initiating cell (TIC) sedimentation field-flow fractionation (SdFFF) sorting, 3D Matrigel amplification, and grafting of corresponding TIC colonies on the chick chorioallantoic membrane, specific tumor matrices could be obtained. Protein analysis also revealed that tumors obtained from a population enriched for “activated” TICs lost “stemness” properties and became invasive. [Anal Bioanal Chem] Abstract |