Volume 4.13 | Apr 8

Cancer Stem Cell News 4.13 April 8, 2015
Cancer Stem Cell News
     In this issue: Publications | Industry News | Policy News | Events | Jobs
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TOP STORY
Key Mechanism Identified In Pediatric Bone Cancers that Allows Proliferation of Tumor-Forming Stem Cells
In normal cell growth, the Hippo pathway works as a dam, regulating cell proliferation. Researchers found that the transcription factor of a DNA binding protein called sex determining region Y box 2 (Sox2), which normally maintains cell self-renewal, actually releases the floodgates in the Hippo pathway in osteosarcomas and other cancers, permitting the growth of highly aggressive, tumor-forming stem cells. [Press release from NYU Langone Medical Center discussing online publication in Nature Communications] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Long Noncoding RNA lncTCF7 Promotes Self-Renewal of Human Liver Cancer Stem Cells through Activation of Wnt Signaling
Scientists identified a long noncoding RNA (lncRNA) termed lncTCF7 that is highly expressed in hepatocellular carcinoma tumors and liver cancer stem cells (CSCs). lncTCF7 is required for liver CSC self-renewal and tumor propagation. Mechanistically, lncTCF7 recruits the SWI/SNF complex to the promoter of TCF7 to regulate its expression, leading to activation of Wnt signaling. [Cell Stem Cell] Abstract | Graphical Abstract

Microenvironmental hCAP-18/LL-37 Promotes Pancreatic Ductal Adenocarcinoma by Activating Its Cancer Stem Cell Compartment
Treatment of pancreatic cancer stem cells with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumorigenicity via formyl peptide receptor 2- and P2X purinoceptor 7 receptor-dependent mechanisms, which could be reversed by inhibiting these receptors. [Gut] Abstract

Effective Eradication of Glioblastoma Stem Cells by Local Application of an AC133/CD133-Specific T Cell-Engaging Antibody and CD8 T Cells
Researchers report the development and preclinical evaluation of a recombinant AC133×CD3 bispecific antibody which redirects human polyclonal T cells to AC133+ glioblastoma multiforme stem cells, inducing their strong targeted lysis. [Cancer Res] Abstract

FoxM1 Drives a Feed-Forward STAT3 Activation Loop that Promotes Self-Renewal and Tumorigenicity of Glioblastoma Stem-Like Cells
In glioblastoma (GBM), investigators found a positive correlation between expression of FoxM1 and PDGF-A. In GBM stem-like cells (GSC) and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. [Cancer Res] Abstract

Development of a Fluorescent Reporter System to Delineate Cancer Stem Cells in Triple-Negative Breast Cancer
Scientists developed a cancer stem cell (CSC) system utilizing a green fluorescence protein (GFP) reporter for the promoter of the well-established pluripotency gene NANOG. NANOG-GFP+ cells gave rise to both GFP+ and GFP cells, and GFP+ cells possessed increased levels of the embryonic stem cell transcription factors NANOG, SOX2 and OCT4 and elevated self-renewal and tumor initiation capacities. [Stem Cells] Abstract

YAP1 Regulates OCT4 Activity and SOX2 Expression to Facilitate Self-Renewal and Vascular Mimicry of Stem-Like Cells
Scientists showed that the transcriptional co-activator YAP1, which is the oncogenic component of the Hippo signaling pathway, is elevated in the stem-like cells from non-small cell lung cancer and contributed to their self-renewal and ability to form angiogenic tubules. [Stem Cells] Abstract | Press Release

miR-942 Promotes Cancer Stem Cell-Like Traits in Esophageal Squamous Cell Carcinoma through Activation of Wnt/β-Catenin Signaling Pathway
Researchers report that miR-942 is significantly upregulated in esophageal squamous cell carcinoma (ESCC), and miR-942 levels are associated with poor prognosis in ESCC patients. Overexpression of miR-942 promotes, whereas inhibition of miR-942 decreases, the tumor sphere formation, the CD90+ subpopulation cells and the expression of pluripotency associated markers. [Oncotarget] Full Article

In Vitro Evidence for Senescent Multinucleated Melanocytes as a Source for Tumor-Initiating Cells
Investigators showed that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes oncogene-induced senescence by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. [Cell Death Dis] Full Article

Role of Lgr5-Positive Cells in Colorectal Cancer
Researchers report expression of Lgr5, a stem cell marker for the intestine and hair follicle, in some of the colorectal cancer (CRC) cells in the patients. Transduction of several CRC cell lines with this virus selectively killed Lgr5-positive cells, resulting in significant inhibition of the CRC cell growth in vitro and in vivo. [Tumor Biol] Abstract

miR-30 Overexpression Promotes Glioma Stem Cells by Regulating Jak/STAT3 Signaling Pathway
Researchers employed multidisciplinary approaches to investigate the upstream regulators of Janus kinase/signal transducer and activator of transcription (Jak/STAT3) signaling in glioma stem cells (GSCs). miR-30 was found to be overexpressed in the GSCs derived from U-87 MG and primary glioma cells, compared with non-stem-cell-like glioma cells and normal cells. [Tumor Biol] Abstract

Wnt Signaling Regulation of Stem-Like Properties in Human Lung Adenocarcinoma Cell Lines
Scientists examined the function of Wnt/β-catenin signaling in maintaining cancer stem cells in lung adenocarcinoma. Lentivirus-mediated knockdown of β-catenin expression accelerated cell cycle and β-catenin knockdown PC9 cells improve the sensitivity to chemotherapy. [Med Oncol] Abstract

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INDUSTRY NEWS
Solid Tumor Study Investigating Ibrutinib (IMBRUVICA®) in Combination with Anti-PD-L1 Antibody (MEDI4736) Commences in Patients with Relapsed/Refractory Non-Small Cell Lung, Breast and Pancreatic Cancers
Pharmacyclics, Inc. announced the initiation of PCYC-1135-CA, a multi-center study that will investigate the use of ibrutinib (IMBRUVICA®) in combination with MEDI4736. The Phase Ib/II study will examine the safety, tolerability and effectiveness of this investigational combination in individuals with relapsed or refractory non-small cell lung cancer, breast cancer, and pancreatic cancer. [Pharmacyclics, Inc.] Press Release

Cold Spring Harbor Laboratory and North Shore-LIJ Announce Strategic Affiliation to Accelerate Benefits of Cancer Research to Patients
Cold Spring Harbor Laboratory (CSHL) and the North Shore-LIJ Health System announced a strategic affiliation to align CSHL’s world-class cancer research with North Shore-LIJ’s growing network of clinical services encompassing more than 16,000 new cancer cases annually across the New York metropolitan area. [Cold Spring Harbor Laboratory] Press Release

UNC Lineberger Sequences 10,000 Tumors as Part of National Cancer Genomics Effort
The UNC Lineberger Comprehensive Cancer Center is leading a national, multi-year, collaborative effort to characterize the genetic changes in nearly 30 cancer types. Earlier this year, UNC Lineberger hit a milestone in this effort – sequencing 10,000 samples of cancer tumor tissue. [UNC Lineberger] Press Release

$10 Million Gift Establishes Center to Develop Personalized Medicine to Fight Cancer
A $10 million gift from entrepreneurs Emmet and Toni Stephenson and their daughter Tessa Stephenson Brand will further the pioneering efforts of Keck Medicine of the University of Southern California (USC) Professor David B. Agus, MD, to change the way cancer is viewed and treated and forge a path to personalized medicine. [Keck Medicine of USC] Press Release

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POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
 
EVENTS
NEW Stem Cells: From Basic Research to Bioprocessing
June 9-11, 2015
London, United Kingdom

Visit our events page to see a complete list of events in the cancer stem cell community.
 
JOB OPPORTUNITIES
NEW Postdoctoral Fellowship – Signaling and Cancer Dissemination (University Hospital in Brno)

NEW Postdoctoral Position – Cancer Biology (University of Pennsylvania)

Postdoctoral Scholar – Cancer Stem Cell Biology (Case Western Reserve University)

Postdoctoral Position – Cancer Imaging (King’s College London)

Postdoctoral Position – Triple Negative Breast Cancer (King’s College London)

Postdoctoral Fellow – Breast Cancer & Stem Cell Biology (University of Cincinnati)

PhD Positions – Immunological Aspects of Cancer and Allergy (University of Salzburg)

Postdoctoral Positions – Stem Cell and Cancer (Brigham & Women’s Hospital)


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