|Cancer Stem Cell News 8.17 May 8, 2019|
Scientists performed metabolomics and metabolite tracing analyses, which revealed that tumor-initiating cells have highly elevated methionine cycle activity and transmethylation rates that are driven by MAT2A. High methionine cycle activity caused methionine consumption to far outstrip its regeneration, leading to addiction to exogenous methionine. [Nat Med]
Investigators report that loss of methylthioadenosine phosphorylase (MTAP) resulted in profound epigenetic reprogramming characterized by hypomethylation of PROM1/CD133-associated stem cell regulatory pathways. MTAP deficiency promoted glioma stem-like cell formation with increased expression of PROM1/CD133 and enhanced tumorigenicity of glioblastoma (GBM) cells and was associated with poor prognosis in GBM patients. [Cancer Res]
RAS induced expression changes that promoted loss of cell identity and acquisition of stemness in a paracrine manner and these changes resulted in reprogramming when combined with reprogramming factors. When cells carried cooperating oncogenic defects, RAS drove cells into an incompatible cellular fate of malignancy. [Stem Cell Reports]
Investigators perfected a cell system of stable, primary lines from human colorecttal carcinoma (CRC) showing that they possessed the full complement of ex– and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). They showed how tumor-initiating CCSCs could establish faithful orthotopic phenocopies of the original disease, which contained cells that spread into the circulatory system. [EBioMedicine]
The authors developed novel disulfide-crosslinked CLL1-targeting micelles (DC-CTM), which could deliver high concentrations of daunorubicin (DNR) into both bulk leukemia cells and leukemia stem cells. Compared to free DNR, DC-CTM-DNR had a longer half-life, increased DNR area under the curve concentration by 11-fold, and exhibited a superior toxicity profile. [Nanomedicine]
Scientists explored the susceptibility of acute myeloid leukemia-leukemic stem cells to anti-leukemic effect of L-asparaginase as well as the role of the two major cell types that constitute the bone marrow microenvironment, i.e., mesenchymal stromal cells and monocytes/macrophages. [Br J Haematol]
Overexpression of protein arginine methyltransferase 1 (PRMT1) was observed in esophageal tumor initiating cells (TICs) purified by magnetic sorting of adherent and spheroid ECA109/TE1 cells. The increased level of PRMT1 in TICs facilitated the expression of TIC markers, stem cell-like properties, resistance to chemotherapy, tumorigenicity and increased their percentages in eophageal squamous cell carcinoma samples. [Cell Death Dis]
To model the head and neck cancer phenotype, researchers created unique Pot1b and p53 null mutant models which allowed genetic lineage tracing of two distinct stem cell populations. Loss of Pot1b expression depleted stem cells via ATR/Chk1/p53 signaling. [Mol Cancer Res]
The authors revealed that tumor-initiating cells showed 27 up-regulated transcripts compared with control cells. The newly identified genes include those coding for PAX8 and FOSB as well as FGF22, whose expressions are known to increase in developing embryos. [Carcinogenesis]
Acute myeloid leukemia cells from sine oculis homeobox (Six)1-knockdown (KD) mice displayed a significantly decreased number and function of leukemia stem cells (LSCs), as assessed by the immunophenotype, colony-forming ability and limiting dilution assay. Further analysis revealed the augmented apoptosis of LSCs and decreased expression of glycolytic genes in Six1 KD mice. [Cancer Sci]
Recently, the dysregulation of RNA modification pathways emerged as a contributor to cancer. By modulating cell survival, differentiation, migration and drug resistance, RNA modifications add another regulatory layer of complexity to most aspects of tumorigenesis. [Nat Cell Biol]
The authors discuss the regulatory mechanisms and pathological roles of epithelial-mesenchymal plasticity, with a focus on recent insights into the complexity and dynamics of this phenomenon in cancer. [Dev Cell]
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Tmunity Therapeutics, Inc. announced it has entered into an exclusive licensing and research collaboration with the University of California (UC) San Francisco aimed at advancing novel engineered T cell receptor (TCR) therapies for rare and currently incurable pediatric conditions with high mortality rates. Initially, research will focus on diffuse intrinsic pontine glioma, a rare and highly aggressive brain stem tumor. [Tmunity Therapeutics, Inc.]
Context Therapeutics announced the start of an open-label basket study to evaluate the efficacy and safety of Apristor in advanced gynecological tumors that are progesterone receptor positive (PR+). Preclinical data suggest that Apristor has anticancer activity by blocking the activation of progesterone receptor signaling by progesterone and/or mitogenic growth factors, inhibiting mammosphere formation, and downregulating gene signatures associated with cancer stem cell mobilization and metastasis. [Context Therapeutics]
Moleculin Biotech, Inc. announced additional positive interim safety and efficacy data from its ongoing open label, single arm Phase I/II study of Annamycin in Poland. After receiving a single starting dose of 120 mg/m2 in the first cohort of the dose escalation phase of the trial, two of three patients treated responded sufficiently to qualify for a potentially curative bone marrow transplant. [Moleculin Biotech, Inc.]
The proportion of scientific articles published by academics in South Africa who are black, colored or of Indian origin has risen almost tenfold since the end of apartheid, to about one-third, finds a report on scholarly publishing in the country. [Nature News]
The leaders of the White House Office of Science and Technology, National Institutes of Health, National Science Foundation, National Institute of Standards and Technology, and the Department of Energy’s science division have formed a committee “to address issues facing the US research community,” President Donald Trump’s administration announced. [The Scientist]
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