Cancer Stem Cell News Volume 8.17 | May 8 2019

TOP STORY

Methionine Is a Metabolic Dependency of Tumor-Initiating Cells

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] Abstract

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MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation

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] Abstract

Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency

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] Full Article | Graphical Abstract

Stemness Underpinning All Steps of Human Colorectal Cancer Defines the Core of Effective Therapeutic Strategies

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] Full Article

Daunorubicin-Containing CLL1-Targeting Nanomicelles Have Anti-Leukemia Stem Cell Activity in Acute Myeloid Leukemia

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] Abstract | Graphical Abstract

Acute Myeloid Leukemia Niche Regulates Response to L-Asparaginase

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] Abstract | Full Article

PRMT1 Regulates the Tumor-Initiating Properties of Esophageal Squamous Cell Carcinoma through Histone H4 Arginine Methylation Coupled with Transcriptional Activation

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] Full Article

Paracrine Interaction of Cancer Stem Cell Populations Is Regulated by the Senescence Associated Secretory Phenotype (SASP)

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] Abstract

ROS Control in Human iPS Cells Reveals Early Events in Spontaneous Carcinogenesis

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] Abstract

Six1 Regulates Leukemia Stem Cell Maintenance in Acute Myeloid Leukemia

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] Abstract

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RNA Modifications Regulating Cell Fate in Cancer

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] Abstract

Epithelial-Mesenchymal Plasticity in Cancer Progression and Metastasis

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] Abstract

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Tmunity and UC San Francisco Announce Exclusive License and Research Collaboration to Advance TCR T Cell Therapies for Pediatric Cancers

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.] Press Release

Context Therapeutics and Memorial Sloan Kettering Cancer Center Announce a Phase II Basket Trial for Apristor in PR⁺ Gynecological Cancers

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] Press Release

Moleculin Announces Additional Positive Interim Results in First Cohort of Phase I/II Clinical Studies of Annamycin in Acute Myeloid Leukemia in Europe

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.] Press Release

Black Academics Publish One-Fifth of South Africa’s Research

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] Editorial

White House to Convene Committee to Address Research Obstacles

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] Editorial

NEW Gordon Research Conference: Hormone-Dependent Cancers
August 4-9, 2019
Newry, Maine, United States

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NEW BIH Johanna Quand Professorships for Women Scientists – Open Topic (Stiftung Charité and The Berlin Institute of Health)

NEW Postdoctoral Fellow Position – Stem Cells in Colon Cancer (Vanderbilt University Medical Center)

NEW Postdoctoral Position – Tumor Metabolism, Stem Cell Biology & Circadian Clock Distruption (University of California Irvine)

Principal Investigator – Cancer Research (Zhejang University)

Research Associates – Cell Competition in Cancer (University of Bristol)

Postdoctoral Research Position – Molecular Biology and Cancer Research (Augusta University)

Postdoctoral Fellowship – Cancer and Glioma Stem Cell Biology (Cornell University)

Postdoctoral Fellow – Glioblastoma Multiforme Research (Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellowship – Hematopoietic Stem Cells (Washington University in St. Louis)

Assistant, Associate, or Full Professor – Breast Cancer (University Hospitals Cleveland Medical Center)

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