Cancer Stem Cell News Volume 8.18 | May 15 2019

TOP STORY

Hepatic Leukemia Factor Is a Novel Leukemic Stem Cell Regulator in DNMT3A, NPM1, and FLT3-ITD Triple-Mutated AML

Researchers showed that triple-mutated acute myeloid leukemia (AML) was characterized by high leukemia stem cell (LSC) frequency, an aberrant leukemia specific GPR56^highCD34^low immunophenotype, and synergistic upregulation of hepatic leukemia factor (HLF). Loss of HLF3 via CRISPR/Cas9 significantly reduced the CD34⁺GPR56⁺ LSC compartment of primary human triple-mutated AML cells in serial xenotransplantation assays. [Blood] Abstract

(Ranked by impact factor of the journal)

Prosurvival Kinase PIM2 Is a Therapeutic Target for Eradication of Chronic Myeloid Leukemia Stem Cells

The authors showed that imatinib mesylate resistance of chronic myeloid leukemia stem cells (CMLSCs) was due, at least in part, to maintenance of BAD phosphorylation by PIM2. They found that in CMLSCs, PIM2 expression was promoted by both a BCR-ABL-dependent STAT5-mediated pathway and a BCR-ABL-independent STAT4-mediated pathway. [Proc Natl Acad Sci USA] Abstract

Dual Delivery of HNF4α and Cisplatin by Mesoporous Silica Nanoparticles Inhibits Cancer Pluripotency and Tumorigenicity in Hepatoma-Derived CD133-Expressing Stem Cells

Investigators showed that the treatment of CD133-expressing Huh7 cells with HNF4α-loaded polyethyleneimine-modified mesoporous silica nanoparticles could suppress their proliferation rate, decreased the proportion of CSCs, the expression of stemness-associated genes and increased the expression of mature hepatocyte-associated genes. [ACS Appl Mater Interfaces] Abstract

Combined Bcl-2/Src Inhibition Synergize to Deplete Stem-Like Breast Cancer Cells

Researchers showed that combined Bcl-2/Src inhibition synergized to deplete stem-like cells. While Src inhibition increased pro-apoptotic PUMA, they found that a significant amount interacted with Bcl-2 and Bcl-xL, promoting resistance to cell death. [Cancer Lett] Full Article

Hypoxia-Induced Secretion Stimulates Breast Cancer Stem Cell Regulatory Signaling Pathways

Conditioned media from estrogen receptor (ER)-α positive hypoxic breast cancer cell cultures increased the fraction of CSCs compared to normal growth conditions, as determined using sets of CSC assays and model systems. In contrast, media from ERα-negative hypoxic cell cultures instead decreased this key subpopulation of cancer cells. [Mol Oncol] Full Article

HDAC7-Mediated Control of Tumor Microenvironment Maintains Proliferative and Stemness Competence of Human Mammary Epithelial Cells

HDAC7 could co-localize with H3K27-acetylated domains and its deletion further increased H3K27ac at transcriptionally-active regions. HDAC7 levels were increased in RAS-transformed cells, in which this protein was not only required for proliferation and cancer stem-like cell growth, but also for invasive features. [Mol Oncol] Abstract | Full Article

DNA Methylation of Shelf, Shore and Open Sea CpG Positions Distinguish High Microsatellite Instability from Low or Stable Microsatellite Status Colon Cancer Stem Cells

Eight colorectal cancer (CRC)-CSC lines were isolated from primary CRC tissues, cultured and characterized for aneuploidy, mutational status of CRC-related genes and microsatellite instability. Genome-wide DNA methylation was assessed by MethylationEPIC microarray. [Epigenomics] Full Article

Pam₃CSK₄, a TLR2 Ligand, Induces Differentiation of Glioblastoma Stem Cells and Confers Susceptibility to Temozolomide

The expression of glioblastoma multiforme (GBM) CSC markers diminished in the presence of Pam₃CSK₄ or LPS, thus indicating toll-like receptor (TLR)-dependent differentiation. Interestingly, simultaneous treatment with Pam₃CSK₄ plus temozolomide (TMZ), the reference drug in GBM treatment, significantly increased cell death compared to the effect of the ligand alone, which showed no toxicity, or TMZ alone. [Invest New Drugs] Abstract

HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells

Investigators showed that panobinostat induced apoptosis in both K562 and imatinib-resistant K562 (IR-K562) cells mainly via H3 and H4 histone acetylation, whereas panobinostat targeted CSCs in IR-K562 cells. They found that histone deacetylase (HDAC)1 and HDAC2 knockout cells significantly induced cell apoptosis, indicating that the regulation of HDAC1 and HDAC2 was extremely important in maintaining K562 cell survival. [Int J Mol Sci] Full Article

Distinct Biological Characterization of the CD44 and CD90 Phenotypes of Cancer Stem Cells in Gastric Cancer Cell Lines

Knowledge is limited regarding the expression and characteristics of marker-positive gastric CSCs. Therefore, gastric CSCs from a series of human gastric cancer cell lines using four putative CSC surface markers were used to investigate the underlying mechanisms regulating such subpopulations. [Mol Cell Biochem] Abstract

Down-Regulation of 14-3-3zeta Reduces Proliferation and Increases Apoptosis in Human Glioblastoma

Scientists demonstrated the role of 14-3-3zeta in glioblastoma proliferation, apoptosis, invasion and tumor growth. The expression of 14-3-3zeta in glioblastoma stem cells was also investigated by immunostaining. Apoptosis was significantly higher in the 14-3-3zeta-negative group than in the positive group. [Cancer Gene Ther] Abstract

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Emerging Roles for Polycomb-Group Proteins in Stem Cells and Cancer

Increasing evidence indicates that the polycomb-group (PcG) complexes can positively regulate gene transcription and modify non-histone substrates in multiple biological processes, cellular stages, and cancers. The authors illustrate recent findings in PcG-mediated gene regulation, with special focus on the recently described non-classical functions of PcG complexes in stem cells and cancer. [Trends Biochem Sci] Abstract

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Investigators evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. They emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of CSCs associated to tumor progression. They also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. [Cancers] Full Article

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Cellectar Receives FDA Fast Track Designation for CLR 131 in Relapsed or Refractory Multiple Myeloma

Cellectar Biosciences, Inc. announced that the FDA has granted Fast Track Designation for CLR 131 in fourth line or later relapse/refractory multiple myeloma. CLR 131 is the company’s small-molecule radiotherapeutic phospholipid drug conjugate designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. [Cellectar Biosciences, Inc.] Press Release

Daiichi Sankyo Announces Outcome of FDA Oncologic Drugs Advisory Committee Meeting to Review FLT3 Inhibitor Quizartinib for the Treatment of Patients with Relapsed/Refractory FLT3-ITD AML

Three committee members voted yes and eight committee members voted no when asked if the results from the pivotal Phase III QuANTUM-R study demonstrated that treatment with quizartinib provides a benefit that outweighs the safety risks for patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited] Press Release

Lixte Biotechnology’s LB-100 to Be Evaluated by the National Cancer Institute in a Clinical Study of LB-100’s Ability to Enter Recurrent Glioblastoma Multiforme Brain Tumors

Lixte Biotechnology Holdings, Inc. announced the opening of a pharmacologic study of the ability of its lead clinical compound, LB-100, to enter the brain and penetrate recurrent glioblastoma multiforme tumors in patients in which surgical removal of their cancers is indicated. [Lixte Biotechnology Holdings, Inc.] Press Release

Medicare Issues Proposed Local Coverage Determination That Provides Coverage of Optune^® for Newly Diagnosed Glioblastoma

Novocure announced the Medicare durable medical equipment Medicare Administrative Contractors have issued a proposed local coverage determination that provides coverage of tumor treating fields, or Optune, for newly diagnosed glioblastoma. [Novocure] Press Release

Damon Runyon Cancer Research Foundation Announces New Physician-Scientist Training Award

The Damon Runyon Cancer Research Foundation announced that six physicians with novel approaches to fighting cancer have been named the 2019 recipients of the Damon Runyon Physician-Scientist Training Award. [The Damon Runyon Cancer Research Foundation (American Association for the Advancement of Science)] Press Release

Europe Abandons Plans for ‘Flagship’ Billion-Euro Research Projects

When Martin Lohse, scientific director of the Max Delbrück Center for Molecular Medicine, welcomed participants to the kick-off meeting for a massive biomedical consortium, he wished them well, even though they would be spending their time in the dark. [ScienceInsider] Editorial

Singapore Passes ‘Fake News’ Law Following Researcher Outcry

Singapore’s parliament has passed a law that bans the spreading of “a false statement of fact” that harms the public interest. Researchers and human-rights groups opposed the regulation, and warn that it will stifle academic debate. [Nature News] Editorial

NIH Fears Good-Government Bill Would Hamper Peer Review

The much-admired system to review grant proposals at the National Institutes of Health (NIH) in Bethesda, Maryland, has become the latest flashpoint in a long-running battle between Congress and the executive branch over how the US government manages advisory bodies. NIH’s parent body, the Department of Health and Human Services in Washington, D.C., opposes legislation moving rapidly through Congress that is aimed at making those committees more transparent. [ScienceInsider] Editorial

NEW Gordon Research Seminar: Overcoming Endocrine Resistance and Metastasis in Hormone-Dependent Cancers
August 3-4, 2019
Newry, Maine, United States

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NEW Postdoctoral Position – Cancer Biology (Washington University School of Medicine)

BIH Johanna Quand Professorships for Women Scientists – Open Topic (Stiftung Charité and The Berlin Institute of Health)

Postdoctoral Fellow Position – Stem Cells in Colon Cancer (Vanderbilt University Medical Center)

Postdoctoral Position – Tumor Metabolism, Stem Cell Biology & Circadian Clock Distruption (University of California Irvine)

Principal Investigator – Cancer Research (Zhejiang University)

Research Associates – Cell Competition in Cancer (University of Bristol)

Postdoctoral Research Position – Molecular Biology and Cancer Research (Augusta University)

Postdoctoral Fellowship – Cancer and Glioma Stem Cell Biology (Cornell University)

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

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

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