Cancer Stem Cell News Volume 7.43 | Oct 31 2018

TOP STORY

The SWI/SNF Complex Is a Mechanoregulated Inhibitor of YAP and TAZ

Using a combination of gain- and loss-of-function approaches in several cellular contexts, the authors showed that YAP/TAZ are necessary to induce the effects of the inactivation of the SWI/SNF complex, such as cell proliferation, acquisition of stem cell-like traits and liver tumorigenesis. [Nature] Abstract

(Ranked by impact factor of the journal)

TRIB3 Interacts with Beta-Catenin and TCF4 to Increase Stem Cell Features of Colorectal Cancer Stem Cells and Tumorigenesis

Scientists found that TRIB3 interacts with beta-catenin and TCF4 in intestine cells to increase expression of genes associated with CSCs. Knockdown of TRIB3 reduced colon neoplasia in mice, migration of colorectal cancer cells, and their growth as xenograft tumors in mice. [Gastroenterology] Abstract

Collagen Prolyl 4-Hydroxylase 1 Is Essential for HIF-1α Stabilization and TNBC Chemoresistance

Activation of the P4HA/HIF-1 axis enhanced cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species levels. Inhibition of P4HA1 sensitized triple-negative breast cancer (TNBC) to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived models. [Nat Commun] Full Article

miR-584-5p Potentiates Vincristine and Radiation Response by Inducing Spindle Defects and DNA Damage in Medulloblastoma

miR-584-5p inhibited medulloblastoma growth and prolonged survival of mice in pre-clinical tumor models. miR-584-5p overexpression caused cell cycle arrest, DNA damage, and spindle defects in medulloblastoma cells. [Nat Commun] Full Article

PRMT2 Links Histone H3R8 Asymmetric Dimethylation to Oncogenic Activation and Tumorigenesis of Glioblastoma

The silencing or inactivation of protein arginine methyltransferase 2 (PRMT2) inhibited glioblastoma multiforme cell growth and glioblastoma stem cell self-renewal in vitro, and suppressed orthotopic tumor growth, accompanied with significant deregulation of genes mainly associated with cell cycle progression and pathways in cancer. [Nat Commun] Full Article

Integrated Stress Response Activity Marks Stem Cells in Normal Hematopoiesis and Leukemia

Researchers showed that the integrated stress response (ISR) is uniquely active in hematopoietic stem cells (HSCs) and facilitates their persistence. Activating transcription factor 4 mediates the ISR and is highly expressed in HSCs due to scarcity of the eIF2 translation initiation complex. Primitive acute myeloid leukemia (AML) cells also displayed eIF2 scarcity and ISR activity marked leukemia stem cells in primary AML samples. [Cell Rep] Full Article | Graphical Abstract

The Role of GLI-SOX2 Signaling Axis for Gemcitabine Resistance in Pancreatic Cancer

Using acquired gemcitabine resistant pancreatic cell lines, scientists revealed an important role of the GLI-SOX2 signaling axis for regulation of gemcitabine sensitivity in vitro and in animal models. Down-regulation of GLI transcriptional factors, but not SMO signaling inhibition, reduces tumor sphere formation, a characteristics of tumor initiating cell. [Oncogene] Full Article

Hypoxia‐Driven Paracrine Osteopontin/Integrin αvβ3 Signaling Promotes Pancreatic Cancer Cell Epithelial‐Mesenchymal Transition and Cancer Stem Cell‐Like Properties by Modulating FOXM1

The authors showed that osteopontin (OPN) is highly expressed and secreted in activated pancreatic stellate cells (PSCs) driven by hypoxia, and this process is in a ROS‐dependent manner; in addition, OPN was shown to be involved in the PSC‐induced epithelial‐mesenchymal transition and CSC‐like properties of pancreatic cancer cells. [Mol Oncol] Full Article | Press Release

Oxytetracycline Have the Therapeutic Efficiency in CD133⁺ HCC Population through Suppression CD133 Expression by Decreasing of Protein Stability of CD133

Treatment of spheroid-forming liver CSCs with oxytetracycline effectively decreased the spheroid formation and the CD133⁺ cell population. Oxytetracycline could suppress expression of CD133 without changing of expression of other stem cell-related markers. [Sci Rep] Full Article

Lurbinectedin (PM01183), a Selective Inhibitor of Active Transcription, Effectively Eliminates Both Cancer Cells and Cancer Stem Cells in Preclinical Models of Uterine Cervical Cancer

Lurbinectedin downregulated stem cell-related gene expression, inhibited HDAC1 activity, and effectively eliminated ALDH-high CSCs. [Invest New Drugs] Abstract

Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model

To investigate the biological effect of adding exogenous soluble CR-1 to the CSCs, scientists prepared a C-terminally truncated soluble form of recombinant human CR-1 protein, in which the glycophosphatidylinositol anchored moiety was removed by substitution of a stop codon through site-directed mutagenesis. [Int J Mol Sci] Full Article

The Role of NF-κB and miRNA in Oral Cancer and Cancer Stem Cells with or without HPV16 Infection

Selective over expression of miR-21 and miR-155 and downregulation of miR-34a were demonstrated by HPV⁺ve CSCs which overexpress HPV16 oncogene E6 that is responsible for the maintenance of stemness. [PLoS One] Full Article

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Cancer from the Perspective of Stem Cells and Misappropriated Tissue Regeneration Mechanisms

The authors address the issue of the identity of cancer-initiating cells and the presence of CSCs in growing tumors. They ask are there rare and distinct populations of CSCs in established tumor cell lines, or are all of the cells CSCs? [Leukemia] Full Article

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Rush Receives $5 Million Gift for Cancer Immunotherapy Research

Rush University Medical Center has received a $5 million donation from Chicago philanthropists Robert and Emily King that will accelerate blood cancer immunotherapy research and the development of new treatment options. [Rush University Medical Center] Press Release

Medicenna Provides Positive Interim Update from Phase IIb Trial of MDNA55 in Recurrent Glioblastoma

Medicenna Therapeutics Corp. announced promising interim efficacy and safety results from patients treated at low doses in the on-going Phase IIb clinical trial of MDNA55 in recurrent glioblastoma. [Medicenna Therapeutics Corp.] Press Release

AIVITA Biomedical Enrolls First Patient in Phase II Glioblastoma Trial

AIVITA Biomedical, Inc. announced the enrollment of its first patient in the company’s Phase II clinical trial for newly diagnosed glioblastoma. [AIVITA Biomedical, Inc.] Press Release

Do Authors Comply When Funders Enforce Open Access to Research?

The first large-scale analysis of compliance with open-access rules reveals that up to one-third of articles are not free to read, report Vincent Larivière and Cassidy R. Sugimoto. [Nature News] Editorial

Australia Plans ‘National-Interest’ Test for Research Grants

Australia’s government is set to introduce a ‘national-interest test’ for research projects seeking grant funding from next year. The policy will require that researchers outline how their project will advance the country’s interests, said education minister Dan Tehan in a statement. [Nature News] Editorial

Research Is Often Unpaid in Sub-Saharan Africa

Unpaid research stints are the norm for scientists in sub-Saharan Africa, according to an online survey of 412 academics that spanned six countries. Eighty-five per cent of respondents report having had research positions with no pay. Of those, 33% had spent between one and five years doing research for free, and 4% had spent more than five years doing so. [Nature News] Editorial

Hungarian Association Wins Prize for Promoting Participation of Women in Science

Last April, Eszti Varga was one of 2,400 young women to converge on 120 universities and companies across Hungary as part of Girls’ Day, a campaign aimed at drawing high-school students into science and technology careers. Sponsored by the Association of Hungarian Women in Science, the campaign has attracted some 10,000 participants across the seven years that it has run. [Nature News] Editorial

NEW Developmental, Metabolic and (Epi)Genomic Mechanisms Driving Organogenesis and Tumorigenesis
March 23-24, 2019
Ventura, California, United States

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NEW 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)

Computational Biologist/Bioinformatician – Hematopoiesis (Karolinska Institutet)

Research Assistant – Stem Cell Biology in Blood System Aging and Blood Cancer (The Jackson Laboratory)

Postdoctoral Associate – Hematopoiesis and Leukemia (The Jackson Laboratory)

Postdoctoral Fellowship Positions – Translational Leukemia (Lund University)

Postdoctoral and Research Associate Positions – Chromatin Remodeling Proteins in Normal Stem Cell & Cancer Biology (Johns Hopkins University School of Medicine)

Faculty Positions – Cancer Biology (The Wilmot Cancer Institute)

Postdoctoral Fellow – Leukemic Stem Cell Chemical Systems Medicine (University of Copenhagen)

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