Cancer Stem Cell News Volume 7.49 | Dec 12 2018

TOP STORY

miR-192-5p Silencing by Genetic Aberrations Is a Key Event in Hepatocellular Carcinomas with Cancer Stem Cell Features

Suppressing miR-192-5p in hepatocellular carcinoma (HCC) cells significantly increased multiple CSC populations and CSC-related features through targeting PABPC4. Both TP53 mutation and hyper-methylation of the miR-192 promoter impeded transcriptional activation of miR-192-5p in HCC cell lines and primary CSC⁺ HCC. [Cancer Res] Abstract

(Ranked by impact factor of the journal)

IGFBP7 Induces Differentiation and Loss of Survival of Human Acute Myeloid Leukemia Stem Cells without Affecting Normal Hematopoiesis

Enhancing IGFBP7 by overexpression or addition of recombinant human IGFBP7 (rhIGFBP7) resulted in differentiation, inhibition of cell survival, and increased chemotherapy sensitivity of primary acute myeloid leukemia cells. Adding rhIGFBP7 reduced leukemic stem and/or progenitor survival and reversed a stem-like gene signature, but it had no influence on normal hematopoietic stem cell survival. [Cell Rep] Full Article | Graphical Abstract

KLF4, A Gene Regulating Prostate Stem Cell Homeostasis, Is a Barrier to Malignant Progression and Predictor of Good Prognosis in Prostate Cancer

Scientists propose that genes that control adult stem cell homeostasis in organs with slow turnover, such as the prostate, control cancer fate. One such gene, KLF4, overexpressed in murine prostate stem cells, regulates their homeostasis, blocks malignant transformation, and controls the self-renewal of tumor-initiating cells. [Cell Rep] Full Article | Graphical Absract

Progesterone Receptor Integrates the Effects of Mutated MED12 and Altered DNA Methylation to Stimulate RANKL Expression and Stem Cell Proliferation in Uterine Leiomyoma

Researchers demonstrated that RANKL specifically upregulated leiomyoma stem cell (LSC) proliferation through activation of cyclin D1. RANKL gene transcription was robustly induced by the progesterone agonist R5020, leading to a dramatically higher RANKL expression in leiomyoma compared to adjacent myometrial tissue. [Oncogene] Full Article

Cancer Stem-Like Properties and Gefitinib Resistance Are Dependent on Purine Synthetic Metabolism Mediated by the Mitochondrial Enzyme MTHFD2

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) knockdown or treatment with 5-aminoimidazole carboxamide ribonucleotide reduced the stem-like properties and restored gefitinib sensitivity in these gefitinib-resistant cancer cells. Moreover, overexpression of MTHFD2 in gefitinib-sensitive lung cancer cells conferred resistance to gefitinib. [Oncogene] Full Article

The Proneural Gene ASCL1 Governs the Transcriptional Subgroup Affiliation in Glioblastoma Stem Cells by Directly Repressing the Mesenchymal Gene NDRG1

Scientists report that achaete-scute homolog 1 gene (ASCL1) not only promotes the acquisition of a proneural phenotype in CSCs by inducing a glial-to-neuronal lineage switch but also concomitantly represses mesenchymal features by directly downregulating the expression of N-Myc downstream-regulated gene 1 (NDRG1), which they propose as a novel gene classifier of mesenchymal glioblastomas. [Cell Death Differ] Full Article

MMP14 Empowers Tumor-Initiating Breast Cancer Cells under Hypoxic Nutrient-Depleted Conditions

The authors investigated epithelial-to-mesenchymal transition and proteases in tumor-initiating cells (TICs) and their response to different environments by means of a newly generated immortalized TIC (iTIC) line. With the use of primary CD24⁺CD90⁺CD45⁻ TICs from the mouse mammary tumor virus-polyoma middle T mouse breast cancer model, iTICs were generated by single cell-initiated sphere and subsequent 2D monolayer culture. [FASEB J] Abstract

ALDH1A3 Induces Mesenchymal Differentiation and Serves as a Predictor for Survival in Glioblastoma

As aldehyde dehydrogenase (ALDH) is a novel stem cell marker, increasing numbers of studies have confirmed that high ALDH activity promotes tumorigenesis and progression in cancers. Scientists elucidated the mechanisms by which ALDH1A3 regulated in glioma and provide practical tools for clinical application. [Cell Death Dis] Full Article

Hypoxia‐Inducible Factor‐2α Directly Promotes BCRP Expression and Mediates the Resistance of Ovarian Cancer Stem Cells to Adriamycin

Researchers showed that increased HIF‐2α expression was associated with enhanced stemness of ovarian CSCs and poor outcomes in ovarian cancer patients. OVCAR‐3 and CAOV‐3 sphere‐forming cells with ovarian CSC‐like properties showed strong resistance to adriamycin. [Mol Oncol] Abstract

miR‐125a/b Inhibits Tumor‐Associated Macrophages Mediated in Cancer Stem Cells of Hepatocellular Carcinoma by Targeting CD90

Investigators showed that tumor‐associated macrophages (TAMs) exosomes promoted hepatocellular carcinoma cell proliferation and stem cell properties. Using miRNA profiles assay, they identified significantly lower levels of miR‐125a and miR‐125b in exosomes and cell lysate isolated from TAMs. [J Cell Biochem] Abstract

IL-6 Mediates Platinum-Induced Enrichment of Ovarian Cancer Stem Cells

Scientists demonstrated that IL-6 regulates stemness features of ovarian CSCs driven by ALDH1A1 expression and activity. They showed that platinum induces IL-6 secretion by cancer-associated fibroblasts in the tumor microenvironment, promoting ovaria CSC enrichment in residual tumors after chemotherapy. [JCI Insight] Full Article

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MicroRNAs in Cancer Stem Cells: Biology, Pathways, and Therapeutic Opportunities

The authors review current understanding of how the misexpression of tumor suppressor and oncogenic miRNAs in CSCs sustain their abundance and malignant properties. They discuss how they partly do so by acting on major CSC signaling pathways, including the Wnt, notch, hedgehog, and BMI‐1 pathways. [J Cell Physiol] Abstract

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.

£1.3 Billion Industry/Government Investment in UK Economy and New Partnership Driving Early Disease Detection

Tens of thousands of lives could be saved by pioneering research to detect deadly diseases before symptoms even appear, thanks to a new collaboration between the government and the Life Sciences Industry. The deal will also announce that global biopharmaceutical company UCB is investing £1 billion in research and development, including in a new state-of-the-art facility, continuing the UK’s reputation as a world leading base for global life sciences research and industry. [GOV UK] Press Release

Phase III Trial of Rova-T as Second-line Therapy for Advanced Small-Cell Lung Cancer (TAHOE Study) Halted

AbbVie announced the decision to stop enrollment for the TAHOE trial, a Phase III study evaluating Rovalpituzumab Tesirine (Rova-T) as a second-line therapy for advanced small-cell lung cancer (SCLC). Rova-T is an investigational antibody-drug conjugate targeting the cancer-stem cell-associated delta-like protein 3, which is expressed in more than 80 percent of SCLC patient tumors, where it is prevalent on tumor cells, including cancer stem cells, but not present in healthy tissue. [AbbVie] Press Release

Europe’s AI Researchers Launch Professional Body over Fears of Falling Behind

Some of Europe’s top machine-learning researchers have founded an organization to strengthen capacity in artificial intelligence (AI) technology on the continent. [Nature News] Editorial

Lawsuit Alleges NIH, FDA Let Clinical Trial Sponsors Off the Hook

A former top official at the FDA and a longtime science journalist are suing the agency and the National Institutes of Health (NIH), saying they let clinical trial sponsors off the hook for reporting nearly a decade’s worth of important scientific data. [STAT News] Editorial

NIH to Spend Up to $20 Million on Search for Alternatives to Fetal Tissue for Research

The National Institutes of Health (NIH) wants to fund up to $20 million worth of research into alternatives to using human fetal tissue to study disease, the agency announced. [STAT News] Editorial

NEW 3^rd International Conference on Stem Cells
October 3, 2019
Chania, Crete, Greece

Visit our events page to see a complete list of events in the community.

NEW Assistant Professor – Cancer Biology (Cold Spring Harbor Laboratory)

Tenure-Track/Tenured Faculty – Cancer Biology (University of Chicago)

Research Scientist – Cancer Biology (MD Anderson Cancer Center)

Postdoctoral Position – Cell and Cancer Biology (St. Jude Children’s Research Hospital)

Postdoctoral Fellowship – Cancer Biology (Mayo Clinic)

Postdoctoral Scholar – Cancer Stem Cells and Organoids (Cancer Institute of New Jersey)

Clinical Research Fellow – Stem Cell Biology of Medulloblastoma (University of Oxford)

Postdoctoral Research Fellow – Cancer Stem Cells in Brain Tumors (University of Calgary)

Faculty Positions – Cancer & Stem Cell Biology (Duke-NUS Medical School)

Assistant Professor – Cancer Biology (University of Pennsylvania Perelman School of Medicine)

Postdoctoral Associate – Hematopoiesis and Leukemia (The Jackson Laboratory)

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