Cancer Stem Cell News Volume 6.09 | Mar 8 2017

TOP STORY

SENP1 Promotes Hypoxia-Induced Cancer Stemness by HIF-1α deSUMOylation and SENP1/HIF-1α Positive Feedback Loop

The authors investigated the effect and mechanism of hypoxic microenvironment and hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness. They showed that hypoxia enhanced the stemness of HCC cells and hepatocarcinogenesis through enhancing HIF-1α de-specific small ubiquitin-like modifier (SUMO)-ylation by SENP1 and increasing stabilisation and transcriptional activity of HIF-1α. [Gut] Full Article

(Ranked by impact factor of the journal)

AKR1B1 Promotes Basal-Like Breast Cancer Progression by a Positive Feedback Loop that Activates the EMT Program

Investigators showed that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with basal-like breast cancer (BLBC) and predicts poor prognosis in breast cancer patients. NF-κB up-regulated Twist2 expression, fulfilling a positive feedback loop that activated the epithelial-mesenchymal transition program and enhanced cancer stem cell–like properties in BLBC. [J Exp Med] Full Article

Integrin-β4 Identifies Cancer Stem Cell-Enriched Populations of Partially Mesenchymal Carcinoma Cells

Carcinoma cells with mesenchymal features are often more resistant to therapy and may serve as a source of relapse. Researchers sought to determine whether such cells could be further stratified into functionally distinct subtypes. They found that a basal epithelial marker, integrin-β4, can be used to enable stratification of mesenchymal-like triple-negative breast cancer cells that differ from one another in their relative tumorigenic abilities. [Proc Natl Acad Sci USA] Full Article

IL-33 Promotes Colon Cancer Cell Stemness via JNK Activation and Macrophage Recruitment

Scientists showed that IL-33 is expressed by vascular endothelial cells and tumor cells in the human colon cancer microenvironment. Administration of human IL-33 and overexpression of murine IL-33 enhanced human and murine colon cancer cell growth in vivo, respectively. [Cancer Res] Abstract

CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

Stimulation of CD95/Fas drives and maintains cancer stem cells. Researchers report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. [Cell Rep] Full Article | Graphical Abstract

Fluorinated N,N’-Diarylureas as Novel Therapeutic Agents against Cancer Stem Cells

Investigators examined the effects of novel AMP-activated protein kinase (AMPK) activating compounds on colorectal cancer metastatic and stem cell lines as potential candidates for chemotherapy. They found that activation of AMPK by all fluorinated N,N-diarylureas compounds at micromolar levels significantly inhibited the cell cycle progression and subsequent cellular proliferation. [Mol Cancer Ther] Abstract

Cordycepin Disrupts Leukemia Association with Mesenchymal Stromal Cells and Eliminates Leukemia Stem Cell Activity

The authors showed that cordycepin reduces CD34⁺CD38⁻ cells in U937 and K562 cells and induces Dkk1 expression via autocrine and paracrine regulation in leukemia and mesenchymal stromal/stem cells (MSCs). Cordycepin suppressed cell attachment of leukemia with MSCs and downregulated N-cadherin in leukemia and VCAM-1 in MSCs. [Sci Rep] Full Article

A c-Myc-Regulated Stem Cell-Like Signature in High-Risk Neuroblastoma: A Systematic Discovery (Target Neuroblastoma ESC-Like Signature)

c-Myc dysregulation is hypothesized to account for the ‘stemness’ – self-renewal and pluripotency – shared between embryonic stem cells (ESCs) and adult aggressive tumors. Using high-risk neuroblastoma as a platform, scientists performed a network analysis of transcriptome data and presented a c-Myc subnetwork enriched for genes previously reported as ESC-like cancer signatures. [Sci Rep] Full Article

Prominin-1-Specific Binding Peptide-Modified Apoferritin Nanoparticle Carrying Irinotecan as a Novel Radiosensitizer for Colorectal Cancer Stem-Like Cells

Nanoparticle (NP) chemotherapeutics preferentially accumulate in tumors and are able to target cancer and cancer stem-like cells through cancer cell-specific ligands, making them uniquely suited as radiosensitizers for chemoradiation therapy. Using a biocompatible apoferritin NP, a prominin-1 (PROM1)-targeted NP carrying irinotecan was engineered. The synergistic effect of the NP and irradiation was evaluated in PROM1-overexpressing HCT-116 colorectal cancer cell lines in vitro and in vivo. [Part Part Syst Charact] Abstract

Sulfasalazine Attenuates Evading Anticancer Response of CD133-Positive Hepatocellular Carcinoma Cells

The authors identified a hitherto unknown mechanism to overcome CD133-induced resistance to anticancer therapy. They found that oxidative stress increased CD133 expression in hepatocellular carcinoma, and increased CD133 expression enhanced the capacity of the defense system against reactive oxygen species, thereby playing a central role in resistance to liver cancer therapy. [J Exp Clin Cancer Res] Full Article

Metastatic Breast Cancer Cells Enter into Dormant State and Express Cancer Stem Cells Phenotype under Chronic Hypoxia

Using at least three cycles of 1% O₂ hypoxia and reoxygenation, investigators established and characterized that the hypoxia-resistant human breast cancer cell line chMDA-MB-231 can stably survive under 1% O₂ conditions by entering into dormant state characterized by arrest in G0/G1 phase and low metabolism. [J Cell Biochem] Abstract

Uncovering the Roles of Long Non-Coding RNAs in Cancer Stem Cells

The authors summarize recent studies that focus on how long non-coding RNAs impact tumor occurrence and progression by affecting cancer stem cell self-renewal and differentiation in liver cancer, prostate cancer, breast cancer, and glioma. [J Hematol Oncol] Full Article

Minimal Residual Disease in Melanoma: Circulating Melanoma Cells and Predictive Role of MCAM/MUC18/MelCAM/CD146

Overall and disease-free survival have been correlated with the presence of circulating melanoma cells (CMCs). Specific melanoma antigens, in particular MCAM (MUC18/MelCAM/CD146), could be a potentially useful tool to isolate CMCs as well as be a prognostic, predictive biomarker. [Cell Death Discov] Full Article

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.

Novogen Awarded Grant of up to A$3 Million by Australian Federal Government for Novel Drug Discovery Program

Novogen Limited announced that it has been awarded a grant of up to A$3 million over three years under the Cooperative Research Centre Project scheme managed by the Australian Department of Industry Innovation and Science. The grant has been awarded to fund development of a next-generation anti-tropomyosin program, which is intended to provide potential new therapies for cancer. [Novogen Limited (PR Newswire Association LLC.)] Press Release

Jax Receives Federal Grant to Improve Crispr-Cas9 Accuracy, Efficiency and Reliability

A two-year grant totaling $455,000 from the National Institutes of Health to Michael V. Wiles, Ph.D., senior director of Technology Evaluation and Development at The Jackson Laboratory, will support research to improve the accuracy and efficiency of genome editing for research, drug testing and future therapeutic delivery. [The Jackson Laboratory] Press Release

Open-Data Contest Unearths Scientific Gems — and Controversy

When a prestigious medical journal challenged scientists to analyze data from a pivotal blood-pressure study in search of new findings, hundreds of researchers around the world rushed to sign up. The contest, sponsored by the New England Journal of Medicine, offered scientists a rare opportunity to access detailed trial data that otherwise might have remained proprietary for another year — if not indefinitely. But the competition, whose winners were announced on 7^th March, also illustrates the tension between speeding access to data and protecting the interests of those who laboured to collect them. [Nature News] Editorial

Prominent British Geneticist Offers Defense in Long-Running Misconduct Investigation

A leading UK academic has spoken publicly for the first time about a byzantine saga involving allegations of research misconduct in papers that stemmed from his research group at University College London. Geneticist David Latchman told Nature that although he did not scrutinize some of the papers sufficiently to detect errors, he also did not produce or directly supervise any of the images at the heart of the allegations. [Nature News] Editorial

NEW American Society of Gene & Cell Therapy (ASGCT)
May 10-13, 2017
Washington, D.C., United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Cancer Research (Houston Methodist Research Institute)

Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine)

Postdoctoral Position – Cancer/Normal Stem Cells (Johns Hopkins University)

Postdoctoral Position – Stem Cell and Cancer Biology (Lund University)

Postdoctoral Research Fellow Positions – Biomedical Research (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Fellow – Cancer Stem Cells (Boston Children’s Hospital/Harvard Medical School)

Principal Investigator – Cancer Research and Oncology Drug Discovery (Southern Research Institute)

Research Fellow – Cancer and Stem Cell Biology (National University of Singapore)

Principal Scientist – Oncology (Janssen)

Postdoctoral Research – Cancer Genetics and Epigenetics (Fred Hutchinson Cancer Research Center)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Viruses and Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cell Cycle Control and Tumorigenesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Ubiquitin System and Cancer (Fred Hutchinson Cancer Research Center)

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