Cancer Stem Cell News Volume 8.24 | Jun 26 2019

TOP STORY

Targeting PDGFRα-Activated Glioblastoma through Specific Inhibition of SHP-2-Mediated Signaling

The effects of SHP099 on cell survival of neural progenitor cells, glioblastoma cell lines, and patient-derived glioma stem-like cells were evaluated. Brain and plasma pharmacokinetics of SHP099 and its ability to inhibit SHP-2 signaling were assessed. [Neuro Oncol] Abstract

(Ranked by impact factor of the journal)

Increased Cholesterol Biosynthesis Is a Key Characteristic of Breast Cancer Stem Cells Influencing Patient Outcome

To gain insight into the unique biology of CSCs, scientists developed patient-derived xenograft tumors (PDXs) from ER^– breast cancers from which they isolated mammospheres that were enriched for CSCs. Comparative global proteomic analysis was performed on patient tumor tissues and corresponding PDXs and mammospheres. [Cell Rep] Full Article | Graphical Abstract

Upregulation of IL-6 in CUL4B-Deficient Myeloid-Derived Suppressive Cells Increases the Aggressiveness of Cancer Cells

The CUL4B complex epigenetically repressed IL-6 transcription in myeloid cells. The IL-6 produced by myeloid-derived suppressor cells (MDSCs) rendered cancer cells stem cell-like properties by activating the IL-6/STAT3 signaling. This crosstalk was effectively blocked either by blocking IL-6 in MDSCs or by inhibition of STAT3 activation in tumor cells. [Oncogene] Abstract

Bcl-2/Bcl-xL Inhibition Predominantly Synergistically Enhances the Anti-Neoplastic Activity of a Low-Dose CUSP9 Repurposed Drug Regime against Glioblastoma

Bcl-2/Bcl-xL inhibition exerted synergistic anti-proliferative effects across established, primary cultured and stem-like glioblastoma cells when combined with CUSP9 which had been reduced to only one tenth of its proposed original concentration. The combination treatment also led to enhanced apoptosis with loss of mitochondrial membrane potential and activation of caspases. [Br J Pharmacol] Abstract

Isorhapontigenin (ISO) Inhibits Stem Cell-Like Properties and Invasion of Bladder Cancer Cell by Attenuating CD44 Expression

Investigators revealed that ISO could inhibit stem cell-like phenotype and invasivity of human bladder cancer by specific attenuation of expression of CD44 but not SOX-2, at both the protein transcription and degradation levels. ISO also down-regulated USP28 expression, which in turn reduced CD44 protein stability. [Cell Mol Life Sci] Abstract

Afatinib and Temozolomide Combination Inhibits Tumorigenesis by Targeting EGFRvIII-cMet Signaling in Glioblastoma Cells

Researchers analyzed the effect of afatinib and temozolomide combination on gioblastoma (GBM) cells U87MG and U251 engineered to express wild type epidermal growth factor receptor (EGFR), EGFRvIII or EGFRvIII dead kinase, CSCs isolated from U87 and U87EGFRvIII in vitro. The therapeutic utility of the drug combination was investigated on tumor growth and progression using intracranially injected U87EGFRvIII GBM xenografts. [J Exp Clin Cancer Res] Full Article

Expression of UPR Effector Proteins ATF6 and XBP1 Reduce Colorectal Cancer Cell Proliferation and Stemness by Activating PERK Signaling

Activation of either XBP1 or ATF6 resulted in reduced cellular proliferation and reduced expression of markers of intestinal epithelial stemness. XBP1-mediated loss of stemness and proliferation resulted from crossactivation of PERK-eIF2α signaling and could be rescued by constitutive expression of eIF2α phosphatase GADD34. [Cell Death Dis] Full Article

KRAS Activation in Gastric Adenocarcinoma Stimulates Epithelial-to-Mesenchymal Transition to Cancer Stem-Like Cells and Promotes Metastasis

The authors sought to examine KRAS activation in epithelial-to-mesenchymal transition (EMT) and generation of CSCs. Transduction of nontransformed HFE-145 gastric epithelial cells with oncogenic KRASG12V significantly decreased expression of the epithelial marker E-cadherin, increased expression of the mesenchymal marker vimentin and the EMT transcription factor Slug, and increased migration and invasion of by 15- to 17-fold. [Mol Cancer Res] Abstract

Knockdown of XB130 Restrains Cancer Stem Cell-Like Phenotype through Inhibition of Wnt/β-Catenin Signaling in Breast Cancer

Silencing endogenous XB130 regulated the cancer stem cell-like properties of breast cancer, including the formation of self-renewing spheres and the proportion of breast cancer SP⁺ cells. Mechanistically, scientists indicated that downregulation of XB130 restrained the epithelial-mesenchymal transition and Wnt/β-catenin signaling, so as to weaken the tumor-initiating cell-like phenotype of breast cancer cells. [Mol Carcinog] Abstract

Endothelial Cells Promote 3D Invasion of GBM by IL-8-Dependent Induction of Cancer Stem Cell Properties

Patient-derived glioblastoma (GBM) spheroids were co-cultured with brain endothelial cells (ECs) in microfabricated collagen gels. Integrating these systems with 3D imaging and biochemical assays revealed that ECs increased GBM invasiveness and growth through interleukin-8 (IL-8)-mediated enrichment of CSCs. Blockade of IL-8 inhibited these effects in GBM-EC co-cultures, while IL-8 supplementation increased CSC-mediated growth and invasion in GBM-monocultures. [Sci Rep] Full Article

MicroRNA-448 Inhibits Stemness Maintenance and Self-Renewal of Hepatocellular Carcinoma Stem Cells through the MAGEA6-Mediated AMPK Signaling Pathway

Researchers explored whether or not miR-448 and melanoma-associated antigen 6 (MAGEA6) were involved in the self-renewal and stemness maintenance of hepatocellular carcinoma stem cells. The interaction among miR-448, MAGEA6, and the AMPK signaling pathway was evaluated. [J Cell Physiol] Abstract

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Genetic and Molecular Epidemiology of Adult Diffuse Glioma

The authors focus on the two dominant trends in glioma science: the characterization of diagnostic and prognostic tumor markers and the identification of genetic and other risk factors. An overview of the many challenges still facing glioma researchers is also included. [Nat Rev Neurol] Abstract

MET in Glioma: Signaling Pathways and Targeted Therapies

Investigators highlight progress made in the understanding of MET signaling in glioma and advances in therapies targeting hepatocyte growth factor/MET molecules for glioma patients in recent years, in addition to studies on the expression and mutation status of MET. [J Exp Clin Cancer Res] Full Article

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.

ONO Enters into Exclusive License Agreement with Rafael Pharmaceuticals on CPI-613 (Devimistat), a Cancer Metabolism Inhibitor, and Other Related Compounds

Ono Pharmaceutical Co., Ltd. announced that it entered into an exclusive license agreement with Rafael Pharmaceuticals, Inc. for the development and commercialization of CPI-613, its first-in-class clinical lead compound, which targets cancer metabolism enzymes, as well as its other related compounds. [Ono Pharmaceutical Co., Ltd.] Press Release

Ziopharm Oncology Completes Enrollment of Controlled IL-12 Plus Opdivo^® (Nivolumab) Phase I Combination Trial in Brain Cancer

Ziopharm Oncology, Inc. announced completion of enrollment of the third cohort of a Phase I clinical trial evaluating controlled IL-12, in combination with the PD-1 inhibitor OPDIVO^® for the treatment of recurrent or progressive glioblastoma multiforme in adults. [Ziopharm Oncology, Inc.] Press Release

Daiichi Sankyo Provides Update on FDA Review of Quizartinib for the Treatment of Patients with Relapsed/Refractory FLT3-ITD AML

Daiichi Sankyo Company, Limited announced that the company received a Complete Response Letter from the FDA for the New Drug Application of quizartinib for the treatment of adults with relapsed/ refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited] Press Release

Bioasis Announces FDA Response to Pre-IND Submission

Bioasis Technologies Inc. announced it had received feedback to its pre-Investigational New Drug (IND) submission to the FDA regarding the planned development of xB3-001, the company’s lead investigational candidate to treat brain cancer. [Bioasis Technologies Inc.] Press Release

Proposal to Close UK Mouse-Research Center Is ‘Major Threat’

Leaders and senior scientists at a national mouse-genetics center in the United Kingdom have written an open letter decrying a recommendation to close the facility’s on-site academic research unit. The closure of the MRC Harwell Institute’s Mammalian Genetics Unit – where scientists study disease using animal models – would be “a major threat to mouse genetics in the UK”, says the letter, organized by 14 senior Harwell scientists. [Nature News] Editorial

USPTO Restarts CRISPR Patent Dispute between Broad and UC

The US Court of Appeals for the Federal Circuit ruled last September that patents held by the Broad Institute of MIT and Harvard University were not in conflict with previously submitted patents from the University of California (UC), Berkeley. But the US Patent and Trademark Office (USPTO) has now posted documents declaring interference between them- meaning they may cover overlapping IP. [The Scientist] Editorial

NEW EMBL Conference: Cancer Genomics
November 4-6, 2019
Heidelberg, Germany

Visit our events page to see a complete list of events in the community.

NEW Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

Postdoctoral Scientist – Cancer Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Jak-Stat Signaling in Prostate & Pancreatic Cancer (Medical College of Wisconsin)

Tier I Canada Research Chair – Precision & Molecular Oncology (University of Calgary)

Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University)

Faculty Positions – Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Position – Cancer Biology (Washington University School of Medicine)

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

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

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