Cancer Stem Cell News Volume 8.33 | Aug 28 2019

TOP STORY

Targeting Glioblastoma Stem Cells through Disruption of the Circadian Clock

Scientists showed that glioblastoma stem cells (GSCs), differentiated glioblastoma cells, and non-malignant brain cultures all displayed robust circadian rhythms, yet GSCs alone displayed exquisite dependence on core clock transcription factors, BMAL1 and CLOCK, for optimal cell growth. Downregulation of BMAL1 or CLOCK in GSCs induced cell cycle arrest and apoptosis. [Cancer Discov] Abstract | Press Release

(Ranked by impact factor of the journal)

ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells

Researchers identified a novel signaling loop that induced and maintained glioblastomas (GSCs) consisting of an atypical metalloproteinase, a disintegrin and metalloproteinase domain-like protein decysin 1 (ADAMDEC1), secreted by GSCs. ADAMDEC1 rapidly solubilized fibroblast growth factor (FGF)-2 to stimulate FGF receptor 1 (FGFR1) expressed on GSCs. FGFR1 signaling induced upregulation of Zinc-finger E-box-binding homeobox 1 via ERK1/2 that regulated ADAMDEC1 expression through miR-203, creating a positive feedback loop. [Cancer Discov] Abstract | Press Release

A NIR Probe Tracks and Treats Lung Tumor Initiating Cells by Targeting HMOX2

Investigators discovered heme oxygenase 2 (HMOX2) as a novel biomarker for tumor initiating cells (TICs) and developed a selective small molecule probe TIC probe with near infra-red (TiNIR). TiNIR detected and enriched the functionally active TIC in human lung tumors, and through photoacoustic properties, TiNIR also visualized lung TIC in the patient-derived xenograft model. [J Am Chem Soc] Abstract

ALK^ATI Interacts with C-Myc and Promotes Cancer Stem Cell-Like Properties in Sarcoma

Compared with the other ALK isoforms, ALK^ATI expressed not only in the cytoplasm, but also in the nucleus of sarcoma cells. Functionally, overexpression of ALK^ATI promoted CSC-like properties in sarcoma cells by promoting sphere formation and upregulating the expression of stem cell markers. [Oncogene] Abstract

A Novel Oral Micellar Fenretinide Formulation with Enhanced Bioavailability and Antitumor Activity against Multiple Tumors from Cancer Stem Cells

The authors developed a novel nano-micellar fenretinide formulation called bionanofenretinide (Bio-nFeR), based on drug encapsulation in an ion-pair stabilized lipid matrix, with the aim to raise fenretinide bioavailability and antitumor efficacy. Bio-nFeR displayed marked antitumor activity against lung, colon and melanoma CSCs both in vitro and in tumor xenografts, in absence of mice toxicity. [J Exp Clin Cancer Res] Full Article

Targeting PI3K/Akt/mTOR Pathway Identifies Differential Expression and Functional Role of IL-8 in Liver Cancer Stem Cell Enrichment

Scientists analyzed the bioactivities and the molecular pathways involved in the action of small molecule PI3K/Akt/mTOR pathway inhibitors in comparison with Sorafenib, DNA intercalators and DAPT on CD133/EpCAM positive liver CSCs (LCSCs). Sorafenib, and DNA intercalators led to the enrichment of LCSCs while Rapamycin and DAPT significantly reduced CD133/EpCAM positivity. [Mol Cancer Ther] Abstract

4-Methylumbelliferone Inhibits Cancer Stem Cell Activation and Overcomes Chemoresistance in Ovarian Cancer

Researchers assessed whether 4-methylubelliferone could inhibit in vivo invasion of chemoresistant primary ovarian cancer cells in a chicken embryo chorioallantoic membrane assay. The expression of the hyaluronan (HA) synthases HAS2 and HAS3 was significantly increased in chemoresistant compared to chemosensitive primary ovarian cancer cells isolated from patient ascites. [Cancers] Full Article

Identification of Novel TGF-β Regulated Genes with Pro-Migratory Roles

Investigators performed RNA-sequencing analysis of MCF10A cells and identified 1166 genes that were upregulated and 861 genes that were downregulated by transforming growth factor-β (TGF-β). Gene set enrichment analysis revealed that focal adhesion and metabolic pathways were the top enriched pathways of the up- and downregulated genes, respectively. [BBA-Mol Basis Dis] Abstract

Transcriptomic Analysis of Breast Cancer Stem Cells and Development of a pALDH1A1:mNeptune Reporter System for Live Tracking

The authors performed transcriptomic analysis to identify segregating gene expression in CSCs and non-CSCs, sorted by Aldefluor assay. They observed that among ALDH associated genes, only ALDH1A1 isoform was increased in CSCs. [Proteomics] Abstract

Pheno-Seq – Linking Visual Features and Gene Expression in 3D Cell Culture Systems

Scientists identified characteristic gene expression signatures of epithelial-to-mesenchymal transition that were associated with invasive growth behavior of clonal breast cancer spheroids. Furthermore, they linked long-term proliferative capacity in a patient-derived model of colorectal cancer to a lowly abundant PROX1-positive cancer stem cell subtype. [Sci Rep] Full Article

MicroRNA-598 Inhibits the Growth and Maintenance of Gastric Cancer Stem-Like Cells by Down-Regulating RRS1

The miR-598 expression was examined in CD133⁺ and CD133^– cells. Subsequently, the CD133⁺ cells were subjected to miR-598 mimics, miR-598 inhibitors or RRS1 siRNA to validate the effect of miR-598 on gastric cancer stem-like cell proliferation, colony formation, apoptosis, migration and invasion capacities. [Cell Cycle] Abstract

Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells

Researchers developed an in vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over an eight-month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth, indicating cell transformation. [Cells] Full Article

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Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

The authors provide a comprehensive review of the dormancy-dictated molecular mechanisms, including angiogenic switch, immune escape, cancer stem cells, extracellular matrix remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced p38 signaling pathways. [Cancers] Full Article

Cancer Stem Cell (CSC) Resistance Drivers

The tumor microenvironment is exposed constantly to the nutritional, metabolic and oxygen deprivation; these conditions promote CSC adaptation. Investigators discuss main mechanisms of CSC resistance and suggest some strategies to revoke this important promoter of therapy failure. [Life Sci] Abstract

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Ivy Brain Tumor Center and Salarius Pharmaceuticals Launch Collaborative Partnership to Develop New Cancer Treatment for Glioblastoma

The Ivy Brain Tumor Center at the Barrow Neurological Institute and Salarius Pharmaceuticals, Inc. announced a collaborative partnership to test Salarius’ therapeutic candidate, Seclidemstat, for the treatment of glioblastoma. The organizations will launch what they believe is the most comprehensive pre-clinical study to date, evaluating the effect of targeting lysine-specific histone demethylase 1A, a key enzyme that has increased expression in tumors of brain cancer patients. [Salarius Pharmaceuticals, Inc.] Press Release

iBio and CC-Pharming Expand Business Collaboration in China

iBio, Inc. announced that it has expanded the scope of its business venture with CC-Pharming Ltd. by granting it an exclusive, royalty-bearing commercial license to iBio’s bio-better rituximab product candidates for the territory of China. In addition, the company will grant to CC-Pharming a research license to iBio’s FastPharming™ System and know-how for the evaluation of multiple product opportunities. [iBio, Inc.] Press Release

Bio-Path Announces Patient Dosing in Amended Phase II Prexigebersen Trial in Acute Myeloid Leukemia

Bio-Path Holdings, Inc. announced patient dosing in Bio-Path’s amended Phase II trial of prexigebersen for the treatment of acute myeloid leukemia, as announced in March 2019. The key change in the amended Phase II study is the inclusion of patients with high risk myelodysplastic syndrome and refractory/relapsed AML patients. [Bio-Path Holdings, Inc.] Press Release

Basilea Announces Completion of Patient Enrolment in Phase I Study with Oral BAL101553 in Brain Cancer

Basilea Pharmaceutica Ltd. announced the completion of patient enrolment in its Phase I study with the oral formulation of the novel tumor checkpoint controller BAL101553 in brain cancer patients. The study included 28 patients with progressive or recurrent glioblastoma, the most aggressive primary brain tumor, or high-grade glioma. [Basilea Pharmaceutica Ltd.] Press Release

Genmab Announces Approval of DARZALEX^® (Daratumumab) in Frontline Multiple Myeloma in Japan

Genmab A/S announced that the Ministry of Health, Labor and Welfare in Japan has approved the use of DARZALEX in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. [Genmab A/S] Press Release

Australia Plans to Tackle Foreign Influence at Nation’s Universities

In response to growing concerns in Australia about foreign influence at universities, cyberspying, and a perceived erosion of freedom of speech on campuses, the country’s education minister today announced that a new task force will develop “best-practice guidelines for dealing with foreign interference.” [Science Magazine] Editorial

More Scientists, Institutions with Links to Jeffrey Epstein

A number of scientists and research institutions continued to maintain links with convicted sex offender and financier Jeffrey Epstein after he was sentenced to prison in 2008, BuzzFeed News reported August 26. While some of the payments and meetings he had with members of the research community were already public knowledge, others were identified by the news site through public records requests. [The Scientist] Editorial

Memo to Italy’s President: Your Researchers Need You

Italy’s coalition government ended abruptly, when the nationalist Lega party of deputy prime minister Matteo Salvini announced that it was walking away from its turbulent coalition with the anti-establishment M5S party, known as the Five Star Movement. The collapse is of great concern: a much-delayed funding increase is now on hold, and the political uncertainty adds further threat. [Nature News] Editorial

NSF Graduate Fellowships Disproportionately Go to Students at a Few Top Schools

As this year’s eligible students begin to labor over their applications, it’s worth asking why certain schools come away with dozens of winners each year—and what that means about the academy at large. [ScienceInsider] Editorial

NEW NF-kB, JAK-STAT & MAPK in Health, Disease & Therapy
October 7-11, 2019
Suzhou, China

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

NEW Postdoctoral Researcher – Stem Cells and Cancer (IRB Barcelona)

NEW Postdoctoral Asssociate – Hematopoietic Stem Cells and Disorders (The Jackson Laboratory)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Cancer Progression (NIH/NCI – Center for Cancer Research)

Associate Professor – Immunology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Scientist – Cancer and Leukemia (St. Jude Children’s Research Hospital)

Postdoctoral Fellow – Leukemic Stem Cell Biology (McGill University Health Centre)

Postdoctoral Researcher – Cancer Stem Cells in Glioblastoma (The Institut Curie Research Center)

Postdoctoral Associate – Hematopoietic Stem Cells and Leukemia (The Jackson Laboratory)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

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)

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