Cancer Stem Cell News Volume 7.35 | Sep 5 2018

TOP STORY

Stem Cell Functionality Is Microenvironmentally Defined during Tumor Expansion and Therapy Response in Colon Cancer

Stem cell properties changed in time depending on the cell location. Although chemotherapy enriched for cells with a CSC phenotype, in this context functional stem cell properties were also fully defined by the microenvironment. [Nat Cell Biol] Abstract | Press Release

(Ranked by impact factor of the journal)

Restricted Cell Cycle Is Essential for Clonal Evolution and Therapeutic Resistance of Pre-Leukemic Stem Cells

Researchers showed that self-renewal, clonal evolution and therapeutic resistance were limited to a rare population of pre-leukemic stem cells (pre-LSCs) with restricted cell cycle. They showed that proliferative pre-LSCs were unable to return to a cell cycle-restricted state. Absence of p21 led to proliferation of pre-LSCs, with clonal extinction through loss of asymmetric cell division and terminal differentiation. [Nat Commun] Full Article

Expansion of Cancer Stem Cell Pool Initiates Lung Cancer Recurrence before Angiogenesis

CD133⁺ lung cancer stem cells (LCSCs) were highly enriched in suspensive tumor compared with progressive tumor. The expansion of LCSC pool promoted angiogenesis by increasing the production of CXCL1 and PlGF in CD133⁺ LCSCs, which resulted in lung cancer recurrence. [Proc Natl Acad Sci USA] Abstract

Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-Like Cells

Notch inhibition led to increased proliferation of PROX1-positive colorectal cancer cells but did not affect their ability to give rise to PROX1-negative secretory cells. PROX1 interacted with the nucleosome remodeling and deacetylase complex to suppress the Notch pathway. [Cancer Res] Abstract

Adipose-Derived Stem Cells Enhance Human Breast Cancer Growth and Cancer Stem Cell-Like Properties through Adipsin

Suppression of adipsin-mediated signaling by a specific inhibitor or adipsin knockdown in adipose-derived stem cells significantly decreased the sphere-forming ability and the expression of CSC markers in co-cultured breast cancer patient-derived xenograft cells. [Oncogene] Abstract

Dedifferentiation Process Driven by TGF-Beta Signaling Enhances Stem Cell Properties in Human Colorectal Cancer

Investigators demonstrated that the dedifferentiation process may be an alternative mechanism in acquisition of CSC-like properties in human colorectal cancer cells. They showed that external stimulation with TGF-beta and the induction of TWIST1 converted CD44⁻ non-CSCs into undifferentiated CD44⁺ CSCs, leading to the significant increment of CSCs in xenograft models. [Oncogene] Abstract

Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells

Scientists identified a novel mechanism by which BRG1 regulated glycolysis genes critical for glioma-initiating cells (GICs). BRG1 suppressed the expression of interferon-stimulated genes, which are negatively regulated by STAT3 and regulate tumorigenesis. Inhibiting BRG1 could sensitize GICs to chemotherapeutic drugs, temozolomide and carmustine. [Stem Cells] Abstract

Rab37 Mediates Exocytosis of Secreted Frizzled-Related Protein 1 to Inhibit Wnt Signaling and Thus Suppress Lung Cancer Stemness

Reconstitution experiments indicated that secreted frizzled-related protein-1 (SFRP1) secretion was crucial for Rab37-mediated cancer stemness suppression and treatment with SRPP1 recombinant protein reduced xenograft tumor initiation ability. Clinical results confirmed that concordantly low Rab37, low SFRP1, and high Oct4 stemness protein expression profile could be used as a biomarker to predict poor prognosis in lung cancer patients. [Cell Death Dis] Full Article

High NRF2 Level Mediates Cancer Stem Cell-Like Properties of Aldehyde Dehydrogenase (ALDH)-High Ovarian Cancer Cells: Inhibitory Role of All-Trans Retinoic Acid in ALDH/NRF2 Signaling

CSC-like properties such as high CSC markers, chemoresistance, colony/sphere formation, and tumor growth were significantly inhibited by nuclear factor erythroid 2-like 2 (NRF2)-silencing in ALDH 1A1-high (ALDH-H) cells. All-trans retinoic acid suppressed ALDH1 expression, inhibiting NRF2 activation, which led to the attenuation of CSC-like properties in ALDH-H cells but not in ALDH-low cells. [Cell Death Dis] Full Article

Acetyl-11-Keto-β-Boswellic Acid Suppresses Docetaxel-Resistant Prostate Cancer Cells In Vitro and In Vivo by Blocking Akt and Stat3 Signaling, Thus Suppressing Chemoresistant Stem Cell-Like Properties

Acetyl-11-keto-β-boswellic acid dose-dependently suppressed the chemoresistant stem cell-like properties of PC3/Doc cells, evidenced by a significant decrease in the ability of mammosphere formation and down-regulation of the expression of a number of stemness-associated genes. The activation of Akt and Stat3 signaling pathways was remarkably enhanced in PC3/Doc cells, which contributed to their chemoresistant stem-like phenotype. [Acta Pharmacol Sin] Abstract

Long Non-Coding RNA HOTAIR Promotes the Self-Renewal of Leukemia Stem Cell through Epigenetic Silencing of p15

HOTAIR knockdown reduced infiltration of leukemic blasts, decreased frequency of leukemia stem cells, and prolonged overall survival in MLL-AF9-induced murine leukemia. p15 partially reversed the decrease of colony and proliferation induced by HOTAIR knockdown, suggesting that p15 plays an important role in the leukemogenesis by HOTAIR. [Exp Hematol] Abstract | Graphical Abstract

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Cytokines, Breast Cancer Stem Cells (BCSCs) and Chemoresistance

The authors discuss cytokine regulation on breast cancer chemoresistance. They also summarize the mutually regulatory networks between cytokines and BCSCs in mediating chemoresistance. [Clin Transl Med] Full Article

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Therapeutic Solutions International Completes Phase I Clinical Trial in Advanced Cancer Patients for Right to Try Access of Its StemVacs Product for American Cancer Patients

Therapeutics Solutions International, Inc. announced the completion of a Phase I clinical trial in advanced cancer patients using its StemVacs cellular immunotherapy. The clinical trial was aimed at establishing the safety of StemVacs, an immunotherapeutic cell-based drug that instructs the immune system to seek and destroy cancer stem cells. [Therapeutic Solutions International, Inc.] Press Release

Redx Pharma Announces Way Forward for RXC004

Redx announced that having presented an amended study protocol to the Medicines and Healthcare products Regulatory Agency, the agency has agreed, in principle, with the proposed re-start of the company’s Phase I/IIa clinical study for the porcupine inhibitor, RXC004. [Redx Pharma Plc] Press Release

Google Unveils Search Engine for Open Data

Google has unveiled a search engine to help researchers locate online data that is freely available for use. The company launched the service, saying that it is aimed at “scientists, data journalists, data geeks, or anyone else”. [Nature News] Editorial

Trump Science-Adviser Pick Breezes through Senate Committee Vote

Meteorologist Kelvin Droegemeier is one step closer to becoming director of the White House Office of Science and Technology Policy and science adviser to President Donald Trump. [Nature News] Editorial

Documentary Puts Lens on the Open-Access Movement Upending Scientific Publishing

Jason Schmitt was working at Atlantic Records when the online site Napster disrupted the music industry by making copyrighted songs freely available. Now, the communications and media researcher at Clarkson University in Potsdam, New York, is pushing for a similar disruption of academic publishing with Paywall, a documentary about the open-access movement that debuts in Washington, D.C. [ScienceInsider] Editorial

European Science Funders Ban Grantees from Publishing in Paywalled Journals

Frustrated with the slow transition toward open access in scientific publishing, eleven national funding organizations in Europe turned up the pressure. As of 2020, the group, which jointly spends about €7.6 billion on research annually, will require every paper it funds to be freely available from the moment of publication. [ScienceInsider] Editorial

NEW 3^rd Scientific Workshop on Tumor Microenvironment in the Hematological Malignancies and its Therapeutic Targeting
February 24-26, 2019
London, United Kingdom

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NEW Postdoctoral Position – Cancer Heterogeneity, Plasticity and Metastasis (International Clinical Research Center St. Anne’s University Hospital Brno)

Faculty Position – Cancer Biology (Emory University Hospital)

Research Scientist – Leukemia (MD Anderson Cancer Center)

Research Associate/Senior Research Associate – Acute Myeloid Leukemia (University of Cambridge)

Postdoctoral Fellow – Stem Cells and Cancer Development (Sanford Burnham Prebys Medical Discovery Institute)

PhD Student – Translational Bio-Medicine (German Cancer Research Center)

Postdoctoral Fellow – Cancer Stem Cells in Murine Models of Kidney Cancer and Head and Neck Cancer (Weill Cornell Medicine)

Group Leader Positions – Precision Medicine (Italian Institute for Genomic Medicine)

Postdoctoral Fellow – Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Scholar – Statistical Bioinformatics (The University of Iowa)

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