|Cancer Stem Cell News 6.37 September 20, 2017|
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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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.]
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]
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]
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]
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