Cancer Stem Cell News Volume 6.31 | Aug 9 2017

TOP STORY

RNAi Screen Identifies Essential Regulators of Human Brain Metastasis-Initiating Cells

Researchers identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs). They established a BMIC patient-derived xenotransplantation model as an investigative tool to comprehensively interrogate human brain metastases. Using both in vitro and in vivo RNA interference (RNAi) screens of these BMIC models, they identified SPOCK1 and TWIST2 as essential BMIC regulators. [Acta Neuropathol] Abstract | Press Release

(Ranked by impact factor of the journal)

EZH2 Palmitoylation Mediated by ZDHHC5 in p53 Mutant Glioma Drives Malignant Development and Progression

Investigators identified a novel mechanism through which mutant p53 drives cancer cell survival and malignant growth. They documented overexpression of the zinc finger protein ZDHHC5 in glioma compared to normal brain tissue and identified that this event as tightly correlated with p53 mutations. [Cancer Res] Abstract | Full Article

Autophagy-Dependent Generation of Axin2⁺ Cancer Stem-Like Cells Promotes Hepatocarcinogenesis in Liver Cirrhosis

To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, scientists labeled Axin2⁺ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. [Oncogene] Full Article

Glioblastoma Stem Cells Exploit the αvβ8 Integrin-TGFβ1 Signaling Axis to Drive Tumor Initiation and Progression

Investigators report that the integrin αvβ8 and its latent transforming growth factor β1 (TGFβ1) protein ligand have central roles in promoting niche co-option and glioblastoma initiation. αvβ8 integrin was highly expressed in glioblastoma stem-like cancer cells and was essential for self-renewal and lineage commitment in vitro. [Oncogene] Abstract

Endoglin Is Essential for the Maintenance of Self-Renewal and Chemoresistance in Renal Cancer Stem Cells

The authors discovered an endoglin (CD105)-expressing subpopulation in human renal cell carcinoma xenografts and patient samples with a greater capability to form spheres in vitro and tumors in mice at low dilutions than parental cells. Knockdown of CD105 by short hairpin RNA and CRISPR/Cas9 reduced stemness markers and sphere-formation ability while accelerating senescence in vitro. [Stem Cell Reports] Full Article

SOX2 Is a Marker for Stem-Like Tumor Cells in Bladder Cancer

Investigators found that Sox2, a transcription factor that is well characterized as a marker for stem cells, is upregulated in both mouse and human bladder cancer (BCa). Using s as a reporter of Sox2 transcriptional expression, they demonstrated that Sox2-expressing cells mark a subpopulation of tumor cells that fuel the growth of established BCa. [Stem Cell Reports] Full Article

Complete Acid Ceramidase Ablation Prevents Cancer-Initiating Cell Formation in Melanoma Cells

Researchers used CrispR-Cas9-mediated gene editing to delete the gene encoding for acid ceramidase (AC), ASAH1, in human A375 melanoma cells. ASAH1-null cells lost the ability to form cancer-initiating cells and to undergo self-renewal, which is suggestive of a key role for AC in maintaining malignancy and self-renewal of invasive melanoma cells. [Sci Rep] Full Article

Cancer Stem Cell-Related Gene Expression as a Potential Biomarker of Response for First-in-Class Imipridone ONC201 in Solid Tumors

Scientists demonstrated that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction. A targeted network analysis of gene expression profiles in colorectal cancer cells revealed that ONC201 downregulates stem cell pathways such as Wnt signaling and modulates genes known to regulate self-renewal in colorectal, prostate cancer and glioblastoma. [PLoS One] Full Article | Press Release

YM155 as an Inhibitor of Cancer Stemness Simultaneously Inhibits Autophosphorylation of Epidermal Growth Factor Receptor and G9a-Mediated Stemness in Lung Cancer Cells

The authors investigated the potential mechanism of YM155 against cancer stemness in lung cancer. They observed that epidermal growth factor receptor autophosphorylation was higher in HCC827- and A549-derived tumorspheres than in parental cells; this autophosphorylation induced tumorsphere formation by activating G9a-mediated stemness. [PLoS One] Full Article

Reprogramming to Developmental Plasticity in Cancer Stem Cells

The epigenetic and metabolic modifications necessary to facilitate phenotypic plasticity are first seen in development and can be re-activated both in normal regeneration and in cancer. However, recent research has suggested that plasticity may also expose weaknesses in cancer cells that could be exploited for future therapeutic development. [Dev Biol] Abstract

Salinomycin’s Potential to Eliminate Glioblastoma Stem Cells and Treat Glioblastoma Multiforme

The authors focus on salinomycin’s potential to treat glioblastoma multiforme including its ability to reduce the CSC population, its toxicity to normal brain cells, its mechanism of action, and its potential for combination treatment. [Int J Oncol] Abstract

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

FDA Awards Orphan Status to Brain Cancer Vaccine Developed at Roswell Park Cancer Institute

The FDA has awarded orphan drug status to a promising immunotherapy vaccine developed at Roswell Park Cancer Institute. The FDA notified MimiVax LLC, a Roswell Park spinoff company, that its application for orphan status for SurVaxM as treatment for glioblastoma, a type of brain cancer, had been approved. [Roswell Park Cancer Institute] Press Release

Trovagene Announces FDA Approval of IND for Phase Ib/II Trial of PCM-075 in Patients with Acute Myeloid Leukemia

Trovagene, Inc. announced that the FDA has accepted its Investigational New Drug (IND) Application for PCM-075, a polo-like kinase 1 inhibitor, and has provided authorization to proceed with the treatment of patients with acute myeloid leukemia. [Trovagene, Inc.] Press Release

Thousands across India March in Support of Science

Thousands of scientists, university students and science enthusiasts gathered in dozens of Indian cities to march in support of science — lamenting their country’s low levels of funding for research, and complaining about government promotion of ‘unscientific ideas’. [Nature News] Editorial

FDA Cracks Down on Pioneering Doctor Who Created a Three-Parent Baby

The New York-based doctor who helped a couple have a child using DNA from three people has been told by the FDA that he can’t go ahead with clinical trials meant to test the technique. [MIT Technology Review] Editorial

CRISPR Patent Battle in Europe Takes a ‘Wild’ Twist with Surprising Player

MilliporeSigma, a subsidiary of pharmaceutical giant Merck KGaA of Darmstadt, Germany, has become a new major player in the complicated European patent battles over CRISPR, the revolutionary genome-editing tool. [ScienceInsider] Editorial

Chronic Diseases Spike in Middle East as Conflicts Rage

Across the Middle East, deaths resulting from violence grew by 850% between 1990 and 2015, according to a series of reports published in the International Journal of Public Health. The increase accelerated after 2010, corresponding with the beginning of the Arab Spring movement and wars in Syria and Iraq. At the same time, the authors found, the incidence of many chronic diseases has also risen dramatically. [Nature News] Editorial

Drug Approval Needs a Helping Hand

It’s time for researchers to lend their expertise to expediting the arrival of cutting-edge therapies that are waiting in the wings. [Nature News] Editorial

NEW ICSCB 2018 : 20^th International Conference on Stem Cell Biology
March 12-13, 2018
Miami, Florida, United States

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

NEW Postdoctoral Researcher – Tumorigenesis and Stem Cell Biology (Yale University School of Medicine)

NEW Postdoctoral Fellow – Molecular Mechanisms of Cancer (Max Delbrück Center for Molecular Medicine)

Assistant or Associate Professor – Cancer Immunotherapeutics (City of Hope)

Assistant Professor – Cell Science (University of Manitoba)

Postdoctoral Fellow – Tumor Microenvironment and Cancer Stem Cells (Duke University Medical Center)

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

Postdoctoral Fellow – Cell Signaling and Cancer Biology (Rutgers Cancer Institute of New Jersey)

Postdoctoral Fellowship – Epithelial Stem Cell Biology (University of Michigan Healthcare System)

Research Scientist – Bioinformatics (University of Glasgow)

Faculty Positions – Cancer and Stem Cell Biology (Sun Yat-Sen University)

Postdoctoral Fellows – Cancer Stem Cell Biology (Genome Institute of Singapore)

Research Officers – Cancer Stem Cell Biology (Genome Institute of Singapore)

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