Cancer Stem Cell News Volume 8.11 | Mar 27 2019

TOP STORY

Mesenchymal Niche-Specific Expression of Cxcl12 Controls Quiescence of Treatment-Resistant Leukemia Stem Cells

During chronic myeloid leukemia development, abnormal clusters of colocalized mesenchymal stromal cells (MSCs) and leukemic stem cells (LSCs) formed but disappeared upon Cxcl12 deletion. Moreover, MSC-specific deletion of Cxcl12 increased LSC elimination by tyrosine kinase inhibitor treatment. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

SIRT1/MRPS5 Axis Enhances the Metabolic Flexibility of Liver Cancer Stem Cells

Mitochondrial ribosomal protein S5 (MRPS5) played a critical role for liver CSCs to maintain stemness properties and to participate in tumor progression. Mechanistically, the acetylation status of MRPS5 was directly regulated by the NAD⁺ dependent deacetylase sirtuin-1 (SIRT1), which was abundant in liver CSCs and decreased during differentiation. [Hepatology] Abstract

Low Doses of Decitabine Improve the Chemotherapy Efficacy against Basal-Like Bladder Cancer by Targeting Cancer Stem Cells

Researchers used mouse models, cultured cell lines and patient-derived xenografts to demonstrate that low dose decitabine treatment remarkably enhanced the effects of cisplatin and gemcitabine on basal-like bladder cancer both in vivo and in vitro. These effects were accompanied by decreases in genome-wide DNA methylation, gene re-expression, and changes in key cellular regulatory pathways such as STAT3 signaling. [Oncogene] Abstract

Protective Autophagy Decreases Osimertinib Cytotoxicity through Regulation of Stem Cell-Like Properties in Lung Cancer

Osimertinib-resistant cells exhibited stem cell-like properties, whereas autophagy inhibition decreased the stemness by downregulating the expression of SOX2 and ALDH1A1. Further, the authors found that knockdown of Beclin-1 inhibited the stem cell-like properties and restored osimertinib cytotoxicity. [Cancer Lett] Abstract

Cell Division Cycle 20 (CDC20) Drives Prostate Cancer Progression via Stabilization of β-Catenin in Cancer Stem-Like Cells

CDC20 was enriched in CD44⁺ prostate CSCs. Knockdown of CDC20 could inhibit the expression of stemness-related genes, self-renewal ability, chemo-resistance, invasion capability and tumorigenicity of CD44⁺ prostate CSCs. [EBioMedicine] Full Article

Alpha6-Integrin Regulates FGFR1 Expression through the ZEB1/YAP1 Transcription Complex in Glioblastoma Stem Cells Resulting in Enhanced Proliferation and Stemness

By in vitro approaches supported by analysis from patients’ databases, scientists determined how α6-integrin and fibroblast growth factor receptor 1 (FGFR1) worked in concert to regulate proliferation and stemness of glioblastoma stem cells. They showed that α6-integrin regulated the expression of FGFR1 and its target gene fokhead box M1 via the ZEB1/YAP1 transcription complex. [Cancers] Full Article

Quantitative Characterization of the Regulation of Iron Metabolism in Glioblastoma Stem-Like Cells Using Magnetophoresis

Investigators focused on different iron regulation mechanisms of glioblastoma cancer stem-like cells and non-stem tumor cells using multiple approaches: cell viability, density and magnetophoresis. [Biotechnol Bioeng] Abstract

Epithelial-Mesenchymal Transition Induced Cancer-Stem-Cell-Like Characteristics in Hepatocellular Carcinoma

Researchers indicated that the expression of epithelial-mesenchymal transition (EMT)-related molecules was correlated with CSCs. In vitro studies indicated that EMT activation could induce CSC characteristics. Notch1 was confirmed to mediate the process of EMT-induced CSCs through the interaction with hypoxia inducible factor 1α directly. [J Cell Physiol] Abstract

lncRNA B4GALT1-AS1 Promotes Colon Cancer Cell Stemness and Migration by Recruiting YAP to the Nucleus and Enhancing YAP Transcriptional Activity

Scientists revealed that positive enrichment of stem cell-differentiated signatures and negative embryonic stem cell function and adult tissue stem module were observed in colon cancer (CC) cells with B4GALT1-AS1 knockdown. Furthermore, B4GALT1-AS1 knockdown suppressed stemness-marker expression, the ability of cell spheroid formation, and ALDH1 activity in CC cells. [J Cell Physiol] Abstract

Chromatin Target of Protein Arginine Methyltransferase (CHTOP) Regulates Invasion, Chemoresistance, and Stemness in Epithelial Ovarian Cancer

Investigators showed that CHTOP knockdown significantly reduced the migration and invasion ability of OV-90 and SK-OV-3 cells, while colony formation assay and apoptosis detection showed that CHTOP knockdown markedly sensitized OV-90 and SK-OV-3 cells to cisplatin treatment by inducing apoptosis. Additionally, CHTOP silence also remarkably weakened the stemness of OV-90 and SK-OV-3 through inhibiting the protein expressions of several transcriptional or surface markers of CSCs. [Biosci Rep] Abstract | Full Article

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Role of OCT4 in Cancer Stem-Like Cells and Chemotherapy Resistance

Although the majority of the studies in CSCs report a positive association between the expression of octamer-binding transcription factor 4 (OCT4) and chemoresistance and an inverse correlation between OCT4 and clinical prognosis, there are studies rebuking these findings, possibly due to the sparsity of stem cells within tumors and the heterogeneity of tumors. [Biochim Biophys Acta] Abstract

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Moleculin Announces Positive Interim Results in First Cohort of Phase I/II Clinical Studies of Annamycin in Acute Myeloid Leukemia in the US and in Poland

Moleculin Biotech, Inc. announced positive interim safety and efficacy data from two ongoing open label, single arm Phase I/II studies of Annamycin. In the first study, being conducted in the US, four patients have completed treatment at 100 mg/m² with no significant adverse events related to Annamycin, and the study will now proceed to the next higher dose of 120 mg/m². [Moleculin Biotech, Inc.] Press Release

Oxford Biomedica Notes the Japanese Approval of Kymriah^® (Tisagenlecleucel), the First CAR-T Cell Therapy Authorised in Asia

Oxford Biomedica plc noted an announcement by Novartis that Japan’s Ministry of Health, Labor and Welfare has approved Kymriah^® for the treatment of two distinct indications – CD19-positive relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia and CD19-positive r/r diffuse large B-cell lymphoma. [Oxford Biomedica plc] Press Release

ExCellThera Announces Clearance by FDA and Health Canada for ECT-001 in New Clinical Trials in United States and Canada for the Treatment of Leukemia

ExCellThera Inc. announced that its lead technology, ECT-001, will be used as part of two new clinical trials in patients with high-risk leukemia. The announcement follows the recent clearance of the company’s Investigational New Drug application by the FDA and of a clinical trial application by Health Canada, in each case for the use of ECT-001 to treat patients with high-risk leukemia and myelodysplasia. [ExCellThera Inc.] Press Release

Aptose Announces FDA Allowance of Investigational New Drug Application for CG-806

Aptose Biosciences Inc. announced that the FDA completed their review of the company’s Investigational New Drug (IND) submission for CG-806. Aptose has been granted IND allowance to initiate its Phase I clinical trial, which is a Phase I, multicenter, open label, dose-escalation study with expansions to assess the safety, tolerability, PK, and preliminary efficacy of CG-806 in patients with chronic lymphocytic leukemia or non-Hodgkin lymphomas. [Aptose Biosciences Inc.] Press Release

Duke University Settles Research Misconduct Lawsuit for $112.5 Million

Duke University will pay $112.5 million to the U.S. government to settle a lawsuit brought by a former employee who alleged that the university included falsified data in applications and reports for federal grants worth nearly $200 million. The university will also take several steps “to improve the quality and integrity of research conducted on campus,” including the creation of a new advisory panel that will provide recommendations to the president, the Durham, North Carolina, institution said in a statement. [ScienceInsider] Editorial

Top US Institutes Still Aren’t Reporting Clinical-Trial Results on Time

Many leading US universities are breaking the law by failing to make public the results of clinical trials. A report found that 25 of the 40 universities that sponsor the most trials in the United States did not post study results on a public, government register within 12 months of completion, as is required by US law. [Nature News] Editorial

As Elsevier Falters, Wiley Succeeds in Open-Access Deal Making

Over the last few years, Project DEAL, a consortium that represents around 700 academic institutions in Germany, has been in negotiations for nationwide licensing agreements with three of the largest scholarly publishers—Elsevier, Springer Nature, and Wiley. [The Scientist] Editorial

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November 8-12, 2019
Boston, Massachusetts, United States

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NEW Research Fellow – Developmental Biology & Cancer (University College London)

NEW Postdoctoral Fellow – Glioblastoma Multiforme Research (Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellowship – Hematopoietic Stem Cells (Washington University in St. Louis)

Assistant, Associate, or Full Professor – Breast Cancer (University Hospitals Cleveland Medical Center)

Lecturer – Developmental Biology and Cancer (University College London)

Postdoctoral Associate – 3D Epigenetic Landscape at Single Cell Level (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral & Research Associate Positions – Cancer, Cancer Stem Cells, Normal Development, and Aging (Johns Hopkins University)

Faculty Position – Prostate Cancer Biology and Cancer Epigenetics (Northwestern University Feinberg School of Medicine)

Postdoctoral Positions – Stem Cell and Cancer Biology (Columbia University Irving Medical Center)

Tenure Track Faculty Position – Cancer Biology & Therapeutics (Geisel School of Medicine at Dartmouth)

Postdoctoral Position – Ovarian Cancer Stem Cells (University of Minnesota)

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