Cancer Stem Cell News Volume 5.08 | Mar 2 2016

Pharmacological Targeting of the Histone Chaperone Complex FACT Preferentially Eliminates Glioblastoma Stem Cells and Prolongs Survival in Preclinical Models
To identify improved therapeutic possibilities, investigators combined the EGFR/HER2 inhibitor lapatinib with a novel small molecule, CBL0137, which inhibits facilitates chromatin transcription (FACT), a histone chaperone complex predominantly expressed in undifferentiated cells. [Cancer Res] Abstract

Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-Like Prostate Cancer Cells in the Bone Marrow
The authors observed that cyclin A1 protein expression was relatively higher in prostate cancer metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase, a key enzyme that directly regulates the local balance of androgens to estrogens. [Cancer Res] Abstract

Non-Migratory Tumorigenic Intrinsic Cancer Stem Cells Ensure Breast Cancer Metastasis by Generation of CXCR4 Migrating Cancer Stem Cells
Scientists showed that unlike highly metastatic cancer stem cells (mCSCs) residing in the breast tumor disseminating/peripheral regions, tumorigenic intrinsic CSCs (iCSCs) populate the inner mass of the tumor and are non-migratory. However iCSCs, via paracrine signaling, induce conversion of non-stem cancer cells to CSCs that are identical to the previously reported mCSCs, and in contrast to iCSCs, express chemokine receptor, chemokine receptor 4 (CXCR4), which is crucial for their metastatic potential. [Oncogene] Abstract

P-Rex1 Promotes Resistance to VEGF/VEGFR-Targeted Therapy in Prostate Cancer
Researchers observed that cancer stem cells isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Resistance was mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involved the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. [Cell Rep] Full Article | Graphical Abstract

ISG15 Predicts Poor Prognosis and Promotes Cancer Stem Cell Phenotype in Nasopharyngeal Carcinoma
Scientists identified interferon-stimulated gene 15 (ISG15) as a differentially expressed gene in nasopharyngeal carcinoma (NPC) and validated its overexpression in NPC samples and cells. High ISG15 levels in NPC tissues were correlated with more frequent local recurrence and shorter overall survival and disease-free survival. [Oncotarget] Full Article 

Epigallocatechin-3-Gallate Targets Cancer Stem-Like Cells and Enhances 5-Fluorouracil Chemosensitivity in Colorectal Cancer
Researchers investigated the chemosensitizing effects of epigallocatechin-3-gallate in 5-fluorouracil-resistant colorectal cancer cells and spheroid-derived cancer stem cells, and interrogated the underlying molecular mechanisms responsible for its chemopreventive activity. [Oncotarget] Full Article

Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying γ-Secretase Inhibitors
Investigators demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of cancer stem cells that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. [Mol Ther] Abstract | Full Article

Metformin Attenuates Transforming Growth Factor Beta (TGF-β) Mediated Oncogenesis in Mesenchymal Stem-Like/Claudin-Low Triple Negative Breast Cancer
Using several mesenchymal stem-like/claudin-low breast cancer cell lines, researchers showed that TGF-β elicits significant increases in cellular proliferation, migration, invasion, and motility, whereas these effects can be abrogated by a specific inhibitor against TGF-β receptor I and the anti-diabetic agent metformin, alone or in combination. [Cell Cycle] Abstract

Short-Term Differentiation of Glioblastoma Stem Cells Induces Hypoxia Tolerance
The authors cultured glioblastoma stem cells from three patient biopsies and exposed these and their differentiated progeny to acute hypoxia while monitoring intracellular calcium and mitochondrial membrane potential. [Neurochem Res] Abstract | Full Article

Cancer Stem Cells and Tumor Immunoediting: Putting Two and Two Together
Although cancer immunity is a rapidly evolving field, the role of the immune system in cancers is yet to be fully decoded. However, the modern concept of immunoediting in cancer has enabled researchers to see things in a new perspective. The cancer stem cells, being at the highest level of tumor hierarchy, are believed to be poorly immunogenic like their normal counterparts. [Expert Rev Clin Immunol] Abstract | Full Article

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La Jolla Institute Receives $5 Million Gift from Pfizer
La Jolla Institute for Allergy and Immunology has received a $5 million gift, which will help establish the Mission Support for Cancer Immunology and Oncology Research. The Institute will use the majority of the funds to establish the Pfizer Endowed Chair in Cancer Immunology and Oncology and support research on the immune system and oncology. [La Jolla Institute for Allergy and Immunology] Press Release

Juno Therapeutics, Seattle Cancer Care Alliance and Fred Hutchinson Cancer Research Center Announce New Immuno-Oncology Clinical Trials Unit
Juno Therapeutics, Inc. and Fred Hutchinson Cancer Research Center announced the creation of a new, best-in-class clinical trials unit dedicated to immuno-oncology. [Juno Therapeutics, Inc.] Press Release

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NEW Translational Research Scientist – Hematology and Oncology (University of Chicago)

Postdoctoral Fellowship – Structures of Proteins Involved in Cancer Metastasis (European Molecular Biology Laboratory)

Full Professorship – Tumor Immunology (German Cancer Research Center)

Junior Professorship – Imaging and Radiation Oncology (German Cancer Research Center)

Postdoctoral Fellowship – Cancer Stem Cell Biology (Fred Hutchinson Cancer Research Center)

PhD Studentship – Various Positions in Cancer (Virginia Commonwealth University)

Faculty Position – Cancer Research (Various Areas) (The Jackson Laboratory)

Postdoctoral Fellowship – Cancer Epigenomics (Princess Margaret Cancer Centre )

Faculty Position – Radioimmunotherapy (Fred Hutchinson Cancer Research Center)

Research Scientist – Hematopoietic Stem Cell Transplantation (University of Chicago)

Staff Scientist – Cell Therapy Process Development (Fred Hutchinson Cancer Research Center)

Post-Doc Fellowship – Bioinformatics RNA Biology and Cancer (German Cancer Research Center)

Post-Doc Fellowship – Genetics and Genomics of Stem Cells (Albert Einstein College of Medicine of Yeshiva University)

Professor – Cancer Immunotherapy (Stanford Cancer Institute)

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