Cancer Stem Cell News Volume 7.31 | Aug 8 2018

TOP STORY

HNF1A Is a Novel Oncogene that Regulates Human Pancreatic Cancer Stem Cell Properties

Levels of HNF1A and its target genes were found to be elevated in pancreatic cancer stem cells (PCSCs) and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, decreased PCSC marker expression, and downregulation of POU5F1/OCT4 expression. Depletion of HNF1A in xenografts impaired tumor growth and depleted PCSC marker-positive cells in vivo. [Elife] Abstract

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Immunoregulatory Protein B7-H3 Regulates Cancer Stem Cell Enrichment and Drug Resistance through MVP-Mediated MEK Activation

Investigators reported a novel finding that upregulation of B7-H3 increased the breast cancer stem cell population and promoted cancer development. B7-H3 expression increased the stem cell population by binding to major vault protein (MVP) which regulated the activation of the MAPK kinase pathway. Depletion of MVP blocked the activation of MEK induced by B7-H3 and dramatically inhibited B7-H3 induced stem cells. [Oncogene] Abstract

Poly(Ethylene Glycol)-Poly(Lysine) Block Copolymer–Ubenimex Conjugate Targets Aminopeptidase N and Exerts an Antitumor Effect in Hepatocellular Carcinoma Stem Cells

Scientists developed a poly(ethylene glycol)–poly(lysine) block copolymer–ubenimex conjugate (PEG-b-PLys(Ube)) to increase the efficacy of reagents in aminopeptidase N (APN)/CD13⁺ CSCs. Exposure to PEG-b-PLys(Ube) increased the intracellular reactive oxygen species concentration by inhibiting APN enzyme activity, permitting the induction of apoptosis and attenuation of hepatocellular carcinoma cell proliferation. [Oncogene] Abstract | Press Release

Inhibition of Autophagy Increases Susceptibility of Glioblastoma Stem Cells to Temozolomide by Igniting Ferroptosis

Researchers suggested that, in vitro, impairing the autophagic process with quinacrine, a compound able to cross the blood-brain barrier, increased glioblastoma stem-like cell (GSC) susceptibility to temozolomide. Death of GSCs was apparently due to the iron dependent form of programmed cell death characterized by the accumulation of lipid peroxides called ferroptosis. [Cell Death Dis] Full Article

Suppression of Breast Cancer Stem Cells and Tumor Growth by the RUNX1 Transcription Factor

Breast CSCs (BCSCs) sorted from pre-malignant breast cancer cells exhibited decreased RUNX1 levels, while ectopic expression of RUNX1 suppressed tumorsphere formation and reduced the BCSC population. RUNX1 ectopic expression in breast cancer cells reduced migration, invasion and in vivo tumor growth in mouse mammary fat pad. [Mol Cancer Res] Abstract

Stroma-Derived IL-6, G-CSF and Activin-A Mediated Dedifferentiation of Lung Carcinoma Cells into Cancer Stem Cells

Using a elegant co-culture cellular system, researchers were able to prove that nutrients and oxygen deprivation activated non-malignant stromal fibroblasts, which in turn established with tumor cells a paracrine loop mediated by interleukine-6 (IL-6), activin-A and granulocyte colony-stimulating factor (G-CSF), that drove subsequent tumor formation and cellular dedifferentiation. [Sci Rep] Full Article

Enrichment of Cancer Stem Cells via β-Catenin Contributing to the Tumorigenesis of Hepatocellular Carcinoma

Serum-free cultured Hepa1–6 cells demonstrated self-renewal, spheroid formation, higher EpCAM expression, increased Hoechst-33342 efflux, and upregulated Wnt/β-catenin signaling. Mice injected with Hepa1–6 CSC spheroids showed aggressive tumor initiation and growth compared with mice injected with control cells. [BMC Cancer] Full Article

STAT3 Exacerbates Survival of Cancer Stem-Like Tumorspheres in EGFR-Positive Colorectal Cancers: RNAseq Analysis and Therapeutic Screening

The authors discovered that signal transducer and activator of transcription 3 (STAT3) inhibition using homoharringtonine and STAT3 knockdown significantly reduced the formation and survival of HT29-derived tumorspheres. They also observed that STAT3 phosphorylation was regulated by epidermal growth factor to induce platelet-derived growth factor A and Wnt signaling cascades. [J Biomed Sci] Full Article

Chemosensitizing Effect of Honokiol in Oral Carcinoma Stem Cells via Regulation of IL-6/Stat3 Signaling

Investigators showed that honokiol reduced the secretion of IL-6 and phosphorylation of STAT3, and that honokiol-inhibited self-renewal, invasion and colony formation were reversed by administration of IL-6. Their data demonstrated that honokiol was able to potentiate the effect of Cisplatin, leading to a lower proportion of oral carcinoma stem cells and decreased cancer stemness features. [Environ Toxicol] Abstract

Esculentoside A Suppresses Breast Cancer Stem Cell Growth through Stemness Attenuation and Apoptosis Induction by Blocking IL-6/STAT3 Signaling Pathway

Esculentoside A (EsA) caused proliferation and mammosphere formation inhibition of breast CSCs, induced breast CSC apoptotic death, and suppressed the growth of tumors generated from breast CSCs significantly. IL-6/STAT3 pathway proteins including IL-6, phosphorylated STAT3, and STAT3 were downregulated significantly in EsA-treated breast CSCs and tumor tissues. [Phytother Res] Abstract

OCT4 Directly Regulates Stemness and Extracellular Matrix-Related Genes in Human Germ Cell Tumors

Conditional knockdown of OCT4 in germ cell tumour (GCT) cell lines reduced cell proliferation by affecting both cell cycle and death. Knockdown of OCT4 also reduced stemness of GCTs, as assessed by the expression of other stemness factors, alkaline phosphatase staining, and tumor sphere formation ability. [Biochem Biophys Res Commun] Abstract

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Targeting Cancer Stem Cells and Their Niche: Perspectives for Future Therapeutic Targets and Strategies

The authors summarize recent advances in CSC research including the characterization of their genetic and epigenetic features, metabolic specialities, and crosstalk with aging-associated processes. Potential strategies for targeting CSCs, and their niche, by regulating CSCs plasticity, or therapeutic sensitivity is discussed. [Semin Cancer Biol] Abstract

Replication Stress Response in Cancer Stem Cells as a Target for Chemotherapy

Investigators provide an overview of the molecular mechanisms of the replication stress response in cancer cells and CSCs, focusing on the role of CHK1 and some emerging players, such as PARP1 and components of the homologous recombination repair, whose targeting can represent a long-term effective anti-CSC strategy. [Semin Cancer Biol] Abstract

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MD Anderson and Jazz Pharmaceuticals Collaborate to Evaluate Potential Treatment Options for Hematologic Malignancies

The University of Texas MD Anderson Cancer Center and Jazz Pharmaceuticals plc announced a five-year collaboration agreement with a goal of evaluating therapies for multiple hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndromes. [The University of Texas MD Anderson Cancer Center] Press Release

Regeneron and bluebird bio Announce Collaboration to Discover, Develop and Commercialize New Cell Therapies for Cancer

Regeneron Pharmaceuticals, Inc. and bluebird bio, Inc. announced a collaboration to apply their respective technology platforms to the discovery, development and commercialization of novel immune cell therapies for cancer. [Regeneron Pharmaceuticals, Inc.] Press Release

FDA Grants Breakthrough Therapy Designation to Daiichi Sankyo’s FLT3 Inhibitor Quizartinib for Relapsed/Refractory FLT3-ITD AML

Daiichi Sankyo Company, Limited announced that the FDA has granted Breakthrough Therapy designation to Quizartinib, an investigational FLT3 inhibitor, for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited] Press Release

Japanese Medical University Admits to Discriminating Against Female Applicants

A prominent Japanese medical university said yesterday that school administrators have deliberately manipulated entrance exam scores to limit the number of women admitted. [ScienceInsider] Editorial

Embattled French Health-Agency Chief Withdraws Leadership Bid

The chief of France’s national biomedical-research agency INSERM has said that he will not run for a second term, a decision that ends months of uncertainty about his future at the organization. [Nature News] Editorial

NEW Acute Leukemias XVII Biology and Treatment Strategies
February 24-27, 2019
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