Cancer Stem Cell News Volume 6.37 | Sep 20 2017

TOP STORY

Use of CRISPR-Modified Human Stem Cell Organoids to Study the Origin of Mutational Signatures in Cancer

Scientists used CRISPR/Cas9 technology to delete key DNA repair genes in human colon organoids, followed by delayed sub-cloning and whole-genome sequencing. They found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair-deficient colorectal cancers. [Science] Abstract

(Ranked by impact factor of the journal)

Targeting Mitochondrial Oxidative Phosphorylation Eradicates Therapy-Resistant Chronic Myeloid Leukemia Stem Cells

Scientists performed metabolic analyses on both stem cell-enriched and differentiated cells derived from individuals with chronic myeloid leukemia (CML), and they compared the signature of these cells with that of their normal counterparts. Through combination of stable isotope-assisted metabolomics with functional assays, they demonstrated that primitive CML cells rely on upregulated oxidative metabolism for their survival. [Nat Med] Abstract

Induction of Cancer Cell Stemness by Depletion of Macrohistone H2A1 in Hepatocellular Carcinoma

Using hepatocellular carcinomas cell lines researchers found that shRNA-mediated macroH2A1 knock-down induces acquisition of cancer stem cells-like features, including the growth of significantly larger and less-differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxia responses and increased glycolysis. [Hepatology] Abstract

ING5 Activity in Self-Renewal of Glioblastoma Stem Cells via Calcium and Follicle Stimulating Hormone Pathways

Investigators found that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF histone acetyltransferase complexes increased expression of the Oct4, Olig2 and Nestin stem cell markers, promoted self-renewal, prevented lineage differentiation and increased stem cell pools in brain tumor initiating cell populations. [Oncogene] Full Article

DOCK4 Promotes Loss of Proliferation in Glioblastoma Progenitor Cells through Nuclear Beta-Catenin Accumulation and Subsequent MiR-302-367 Cluster Expression

Scientists report an unexpected anti-proliferative role of beta-catenin in non-mitotic differentiated glioblastoma cells. By cell type specific stimulation of miR-302, which directly repressed cyclin D1 and stemness features, beta-catenin was capable to change its known proliferative function. [Oncogene] Abstract

MZF1 and GABP Cooperate with Sox2 in Regulating the Expression of YAP1 in Cancer Cells

Scientists subjected the YAP1 intronic enhancer to scanning mutagenesis to identify all DNA cis-elements critical for enhancer function. They identified two novel transcription factors, GABP and MZF1, which are essential for basal YAP1 transcription. [Stem Cells] Abstract

Telomere DNA Damage Signaling Regulates Cancer Stem Cell Evolution, Epithelial Mesenchymal Transition, and Metastasis

The authors found that loss of TRF2 and Terc expression resulted in telomere DNA damage, severely depleted CD34 + and Lgr6+ cancer stem cells, and induced terminal differentiation of metastatic cancer cells. However a novel cancer stem cell population evolved in primary tumors exhibiting genomic instability, alternative lengthening of telomeres, and epithelial-mesenchymal transition. [Oncotarget] Full Article

SOX9 Regulates Cancer Stem-Like Properties and Metastatic Potential of Single-Walled Carbon Nanotube-Exposed Cells

Researchers linked SOX9, a stem cell associated transcription factor, to the neoplastic-like properties of human lung epithelial cells chronically exposed to a low-dose of single-walled carbon nanotubes (SWCNTs). They found that SOX9 is upregulated in SWCNT-exposed cells, which is consistent with their abilities to induce tumor formation and metastasis in vivo. [Sci Rep] Full Article

WASH Overexpression Enhances Cancer Stem Cell Properties and Correlates with Poor Prognosis of Esophageal Carcinoma

Investigators studied the role of WASP and SCAR Homolog (WASH), a recently identified WASP family member, in human esophageal squamous cell carcinoma (ESCC). Using three human ESCC cell lines, they found that WASH expression was significantly elevated in cancer stem-like cells enriched by sphere formation assay. [Cancer Sci] Abstract

Hsp90α Mediates BMI1 Expression in Breast Cancer Stem/Progenitor Cells through Facilitating Nuclear Translocation of C-Myc and EZH2

The authors demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Heat shock protein 90 (Hsp90), could suppress the self-renewal of breast cancer stem cells by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. [Int J Mol Sci] Full Article

The Metabolic Cross-Talk Between Epithelial Cancer Cells and Stromal Fibroblasts in Ovarian Cancer Progression: Autophagy Plays a Role

Cancer-associated fibroblasts can influence the actual level of autophagy in ovarian cancer cells through the secretion of pro-inflammatory cytokines and the release of autophagy-derived metabolites and substrates. Interrupting the metabolic cross-talk between cancer cells and cancer-associated fibroblasts could be an effective therapeutic strategy to arrest the progression and prevent the relapse of ovarian cancer. [Med Res Rev] Abstract

The Multifaceted Role of Periostin in Priming the Tumor Microenvironments for Tumor Progression

Periostin plays a critical role in establishing and remodeling tumor microenvironments such as the metastatic niche, cancer stem cell niche, perivascular niche, pre-metastatic niche, fibrotic microenvironment and bone marrow microenvironment. The authors summarize the current knowledge of the multifaceted role of periostin in the tumor microenvironments. [Cell Mol Life Sci] Abstract

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

Kiadis Pharma Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for ATIR101^™

Kiadis Pharma N.V. announced that the FDA has granted ATIR101^™, Kiadis Pharma’s lead investigational product for blood cancers, the Regenerative Medicine Advanced Therapy designation. [Kiadis Pharma N.V.] Press Release

FDA Approves Amgen and Allergan’s MVASI^™ (bevacizumab-awwb) For The Treatment Of Five Types Of Cancer

Amgen and Allergan plc. announced that the FDA has approved MVASI^™ for all eligible indications of the reference product, Avastin^®. MVASI is approved for the treatment of five types of cancer, including in combination with chemotherapy for non-squamous non-small cell lung cancer, in combination with chemotherapy for metastatic colorectal cancer, glioblastoma, metastatic renal cell carcinoma in combination with interferon alfa and in combination with chemotherapy for persistent, recurrent, or metastatic carcinoma of the cervix. [Amgen] Press Release

U.S. House Approves 2018 Spending Bills, but Process Far from Finished

The U.S. House of Representatives took a major step toward setting federal science budgets for the 2018 fiscal year. But Congress is still far from the finish line, and final spending levels aren’t likely to be finalized until late this year at the earliest. [ScienceInsider] Editorial

Publishers Go After Networking Site for Illicit Sharing of Journal

A major scientific publishing group is taking aim at a social networking site for allowing researchers to illegally post copies of their journal papers. The International Association of Scientific, Technical, and Medical Publishers in Oxford, U.K., and The Hague, the Netherlands, has written to ResearchGate, a networking website for researchers, to express concerns over its article-sharing practices. [ScienceInsider] Editorial

NEW 7^th in Leukemia Research (NDLR) Meeting
March 25-28, 2018
Brisbane, Australia

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

NEW Postdoctoral Positions – Stem Cell and Cancer Biology (Johns Hopkins University)

Director – Stanford Cancer Institute (Stanford University)

Research Associate – Plasticity and Cancer (University of Cambridge)

Faculty Position – Stem Cell Biology (University of Texas Southwestern Medical Center)

Postdoctoral Position(s) – Cancer and/or Glioma Stem Cell Research (Weill Cornell College of Medicine)

Postdoctoral Scholar – Cancer Stem Cell Research (University of California, Los Angeles G.O. Discovery Laboratory)

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

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)

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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