|Cancer Stem Cell News 8.13 April 10, 2019|
Researchers used RNA sequencing (seq), chromatin immunoprecipitation-seq, and genome-wide CRISPR analysis to map the molecular dependencies of pancreatic cancer stem cells, highly therapy-resistant cells that preferentially drove tumorigenesis and progression. This integrated genomic approach revealed an unexpected utilization of immuno-regulatory signals by pancreatic cancer epithelial cells. [Cell]
Scientists identified ubiquitin-specific protease 9X (USP9X) as a bona fide deubiquitinase of aldehyde dehydrogenase 1A3 (ALDH1A3) in mesenchymal (MES) glioblastoma stem cells (GSCs). USP9X interacted with, depolyubiquitylated, and stabilized ALDH1A3. Moreover, they showed that FACS-sorted USP9Xhi cells were enriched for MES GSCs with high ALDH1A3 activity and potent tumorigenic capacity. [J Clin Invest]
Investigators showed that tumor-associated neutrophils secreted BMP2 and TGF-β2, and triggered miR-301b-3p expression in hepatocellular carcinoma (HCC) cells, subsequently suppressed gene expression of limbic system-associated membrane protein and CYLD lysine 63 deubiquitinase and increased stem cell characteristics in HCC cells. [Hepatology]
The authors described that leukemic stem cells in mast cell leukemia (MCL) resided within a CD34+/CD38– fraction of the clone. Whereas highly purified CD34+/CD38– cells engrafted NSGhSCF mice with fully manifesting MCL, no MCL was produced by CD34+/CD38+ progenitors or the bulk of KIT+/CD34– mast cells. [Leukemia]
While heterozygous induced pluripotent stem cells remained largely similar to wild-type cells, homozygosity for PIK3CAH1047R caused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, up-regulation of stemness markers, and impaired differentiation to all three germ layers in vitro and in vivo. [Proc Natl Acad Sci USA]
Researchers examined two independent high repressor element-1 silencing transcription factor (REST) glioblastoma stem cell (GSC) lines using genome-wide assays, biochemical validations, gene knockdown analysis, and mouse tumor models. Genome-wide transcriptome and DNA-binding analyses suggested the dopamine receptor D2 (DRD2) gene, a dominant regulator of neurotransmitter signaling, as a direct target of REST. [Neuro Oncol]
Scientists reported that the leucine-rich domain (LRD) of neurofibromin inhibited invasion of human glioblastoma cells without affecting their proliferation. Moreover, under conditions tested, the NF1-LRD failed to hydrolyze Ras-GTP to Ras-GDP, suggesting that its suppressive function was independent of Ras signaling. [Oncogene]
The human glioma cell lines and patient derived glioma stem cells were studied in vitro and in vivo, revealing that mesenchymal glioblastoma (GBM) expressed and secreted the highest level of prosaposin (PSAP) among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial-mesenchymal transition-like processes in vivo and in vitro. [J Pathol]
Using genetic approaches targeting G0/G1 switch gene 2 (G0S2) in glioma cells and glioma stem-like cells (GSCs), investigators found that knockdown of G0S2 promoted lipid droplet turnover, inhibited GSC radioresistance, and extended survival of xenograft tumor mice with or without ionizing radiation. In contrast, overexpression of G0S2 promoted glioma cell radiation resistance. [J Exp Clin Cancer Res]
Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), were combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, the authors detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO. [J Nanobiotechnology]
Increased Skp2 expression was observed in prostate cancer cell lines with mesenchymal and CSC-like phenotype compared to their epithelial counterparts. Conversely, the CSC-like phenotype was diminished in cells in which SKP2 expression was silenced. Furthermore, investigators observed that Skp2 downregulation led to the decrease in subpopulation of CD44+CD24– cancer stem-like cells. [Sci Rep]
The authors summarize current findings about links between neural stem cells and cancer stem cells in glioblastoma and discuss current therapeutic approaches, which arise as a result of identifying the cell of origin in glioblastoma. [Cancers]
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Moleculin Biotech, Inc. announced it has successfully expanded the clinical supply of Annamycin for its on-going clinical trials via BSP Pharmaceuticals S.p.A. in Latina, Italy. [Moleculin Biotech, Inc.]
Daiichi Sankyo Company, Limited announced that the FDA has extended the review period for the New Drug Application of quizartinib, an investigational FLT3 inhibitor, currently under priority review for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Ltd]
A damning report that says racism is entrenched at the University of Cape Town has reignited discussions about how to erase the divisive legacy of colonialism at South Africa’s top research institutions. [Nature News]
On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist]
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