Cancer Stem Cell News Volume 7.46 | Nov 21 2018

TOP STORY

IKZF2 Drives Leukemia Stem Cell Self-Renewal and Inhibits Myeloid Differentiation

IKZF2 was highly expressed in leukemic stem cells (LSCs), and its deficiency resulted in defective LSC function. IKZF2 depletion in acute myeloid leukemia cells reduced colony formation, increased differentiation and apoptosis, and delayed leukemogenesis. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

H3K9 Methyltransferases and Demethylases Control Lung Tumor-Propagating Cells and Lung Cancer Progression

Investigators showed that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells. [Nat Commun] Full Article | Press Release

HDAC6 Differentially Regulates Autophagy in Stem-Like versus Differentiated Cancer Cells

Scientists demonstrated that HDAC6 inhibition differentially modulates macroautophagy/autophagy in CSCs as compared to that of differentiated cancer cells. [Autophagy] Abstract

Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer

DCLK1 was identified as the direct target gene for miR-15b and its suppression was associated with self-renewal and tumorigenic properties of DCLK1⁺ tumor-initiating cells. [Stem Cell Reports] Full Article

Androgen Receptor (AR)/miR-520f-3p/SOX9 Signaling Is Involved in the Altering Hepatocellular Carcinoma (HCC) Cell Sensitivity to the Sorafenib Therapy under Hypoxia via Increasing Cancer Stem Cells Phenotype

An in vivo mouse model with orthotopic xenografts of HCC cells validated in vitro data, and a human HCC sample survey confirmed the positive linkage of AR/miR-520f-3p/SOX9 signaling to the CSCs population during HCC progression. [Cancer Lett] Abstract

Synthesis and Discovery of Novel Anti-Cancer Stem Cells Compounds Derived from the Natural Triterpenoic Acids

In order to explore the leading compounds targeting CSCs, 52 analogues of triterpenoic acids were synthesized in this study, whose biological activities were evaluated. Based on the results of tumorsphere assay, two compounds 48 and 51, derived from oleanolic acid, exhibited suppressive effect on elimination of different type of CSCs. Meanwhile, compound 48 and 51 could significantly inhibit the growth of several tumors both in vitro and in vivo. [J Med Chem] Abstract

Apigenin Suppresses the Stem Cell-Like Properties of Triple-Negative Breast Cancer Cells by Inhibiting YAP/TAZ Activity

Investigators demonstrated that apigenin inhibited stemness features of triple-negative breast cancer cells in both in vitro and in vivo assays. [Cell Death Discov] Full Article

Sortilin Inhibition Limits Secretion-Induced Progranulin-Dependent Breast Cancer Progression and Cancer Stem Cell Expansion

In various in vivo-like screening assays, progranulin was identified as a potent cancer stem cell activator, highly secreted in ERα-negative breast cancer as well as in ERα-positive breast cancer under hypoxic adaptation. Progranulin exposure caused dedifferentiation as well as increased proliferation of the cancer stem cell pool, a process that was shown to be dependent on its receptor sortilin. [Breast Cancer Res] Full Article

DLG5 Suppresses Breast Cancer Stem Cell‐Like Characteristics to Restore Tamoxifen Sensitivity by Inhibiting TAZ Expression

Scientists showed that discs large homolog 5 (DLG5) expression is down‐regulated in tamoxifen (TAM)‐resistant breast cancer and cells. DLG5 silencing decreased the sensitivity to TAM and increased the frequency and stemness of CD44⁺/CD24⁻ breast cancer stem cells and TAZ, a transducer of the Hippo pathway, expression in MCF7 cells while DLG5 overexpression had opposite effects. [J Cell Mol Med] Full Article

HMGB1‐RAGE Signaling Facilitates Ras‐Dependent Yap1 Expression to Drive Colorectal Cancer Stemness and Development

Researchers showed that RAGE has direct association with K‐Ras following HMGB1 exposure in colorectal cancer (CRC) cells. HMGB1 exposure led to the proliferation of CRC cells and the expansion of CRC stem cells. [Mol Carcinog] Abstract

Silibinin, a Natural Blend in Polytherapy Formulation for Targeting Cd44v6 Expressing Colon Cancer Stem Cells

A comprehensive prediction and screening of CD44v6 against 1674 lead compounds was conducted. Silibinin was identified as a potential compound targeting CD44v6. In order to substantiate these findings, the cytotoxic effect of 5FU, Silibinin and 5FU+Silibinin was assessed on human colon carcinoma cell line HCT116 derived CD44⁺ subpopulation. [Sci Rep] Full Article

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New Insights into the Mechanisms of Epithelial-Mesenchymal Transition and Implications for Cancer

The authors discuss recent findings on the mechanisms and roles of epithelial-mesenchymal transition (EMT) in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this program. They also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. [Nat Rev Mol Cell Biol] Abstract

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AIVITA Biomedical Announces Treatment of First Two Patients in Phase II Glioblastoma Trial

AIVITA Biomedical announced that it has dosed the first two patients in its Phase II clinical trial in patients with newly diagnosed glioblastoma. The trial is designed to investigate AIVITA Biomedical’s next-generation patient-specific cancer treatment, uniquely targeting the patient’s tumor-initiating cells. [AIVITA Biomedical] Press Release

NOXXON to Launch NOX-A12 with Radiotherapy Clinical Trial in Patients with Brain Cancer

NOXXON Pharma N.V. announced that the company is preparing a new clinical trial combining NOX-A12 with radiotherapy for the treatment of patients with newly diagnosed brain tumors. [NOXXON Pharma N.V.] Press Release

Frustrated Alzheimer’s Researchers Seek Better Lab Mice

The US National Institutes of Health, the UK Dementia Research Institute and Jackson Laboratory — one of the world’s biggest suppliers of lab mice — are among the groups trying to genetically engineer more sophisticated rodents. [Nature News] Editorial

Stop Exploitation of Foreign Postdocs in the United States

A survey reveals some lab heads are using the need for visas to create unacceptable conditions for junior researchers. Some PIs are exploiting the fact that overseas scientists rely on them for continued visas. The responses suggest that senior scientists are using this reliance to force postdocs to work longer hours and endure unacceptable conditions. [Nature News] Editorial

To Catch Misconduct, Journals Are Hiring Research Integrity Czars

Scientific journals’ creation of dedicated positions for rooting out misconduct before publication comes amid growing awareness of such issues, and stems from a recognition that spot-checking and other ad hoc arrangements were insufficient. [STAT News] Editorial

NEW DASCS2019 Stem Cell conference
May 2-3, 2019
Vejle, Denmark

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NEW Postdoctoral Fellowship – Cancer Biology (Mayo Clinic)

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

Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

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

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

Postdoctoral Scientist – Drug Discovery Unit and Molecular Oncology Group (Cancer Research UK Manchester Institute)

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

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

PhD Studentships – Cancer (The Cancer Research UK Manchester Institute)

Postdoctoral Associate – Hematopoiesis and Leukemia (The Jackson Laboratory)

Postdoctoral Fellowship Positions – Translational Leukemia (Lund University)

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