Cancer Stem Cell News Volume 6.05 | Feb 8 2017

TOP STORY

The Cargo Protein MAP17 (PDZK1IP1) Regulates the Cancer Stem Cell Pool Activating the Notch Pathway by Abducting NUMB

PDZKIP1, a small cargo protein overexpressed in tumors, interacted with NUMB through the PDZ-binding domain activating the Notch pathway, leading to an increase in stem cell factors and cancer-initiating-like cells. Identical behavior was mimicked by inhibiting NUMB. [Clin Cancer Res] Abstract

(Ranked by impact factor of the journal)

Downregulation of PCK2 Remodels Tricarboxylic Acid Cycle in Tumor-Repopulating Cells of Melanoma

Researchers showed that mitochondrial phosphoenolpyruvate carboxykinase (PCK2), the hub molecule linking tricarboxylic acid cycle, glycolysis and gluconeogenesis by conversion of mitochondrial oxaloacetate to phosphoenolpyruvate, regulates glucose carbon flow direction in stem-like cells that repopulate tumors. [Oncogene] Abstract

Mutant p53 Oncogenic Functions in Cancer Stem Cells Are Regulated by WIP through YAP/TAZ

Investigators established that the oncogenic activity of mutant p53 (mtp53) is driven by the WASP-interacting protein (WIP). WIP knockdown from mtp53-expressing glioblastoma and breast cancer cells greatly reduced proliferation and growth capacity of cancer stem cell (CSC)-like cells and decreased CSC-like markers. [Oncogene] Abstract

Transforming Growth Factor-β-Induced Plasticity Causes a Migratory Stemness Phenotype in Hepatocellular Carcinoma

Scientists analyzed the effects of transforming growth factor-(TGF)-β on the epithelial-mesenchymal transition (EMT) and stem-related properties of hepatocellular carcinoma (HCC) cells and the potential correlation among those processes. Results indicated that when TGF-β induces EMT in HCC cells, a switch in the expression of stem genes is observed and their stemness potential and migratory/invasive capacity are enhanced. [Cancer Lett] Abstract | Graphical Abstract

Metalloprotease-Disintegrin ADAM12 Actively Promotes the Stem Cell-Like Phenotype in Claudin-Low Breast Cancer

Investigators found that sorted SUM159PT cell populations with high ADAM12 levels had elevated expression of cancer stem cell markers and an increased ability to form mammospheres. ADAM12 knockdown reduced cell migration and invasion, decreased anoikis resistance, and compromised mammosphere formation. [Mol Cancer] Full Article

Dclk1, a Tumor Stem Cell Marker, Regulates Pro-Survival Signaling and Self-Renewal of Intestinal Tumor Cells

The authors found a correlation between doublecortin-like kinase 1 (DCLK1) and pro-survival signaling expression. Intestinal epithelial cells of Apc^Min/+ mice showed increased expression of pro-survival signaling, pluripotency and self-renewal ability. [Mol Cancer] Full Article

Zinc Finger Protein X-Linked (ZFX) Promotes Expansion of EpCAM⁺ Cancer Stem Like Cells in Hepatocellular Carcinoma

Researchers observed that the elevated expression of both ZFX and epithelial cell adhesion molecule (EpCAM) was associated with aggressive clinicopathological features and indicated poor prognosis in patients with hepatocellular carcinoma. ZFX was commonly enriched in liver EpCAM⁺ cancer stem cells. [Mol Oncol] Abstract | Full Article

Small G Protein Rac GTPases Regulate the Maintenance of Glioblastoma Stem-Like Cells In Vitro and In Vivo

To investigate whether Rac proteins can serve as therapeutic targets for glioblastoma, especially for glioblastoma stem cells or stemloids, the authors examined the potential roles of Rac1, Rac2 and Rac3 on the properties of tumorspheres derived from glioblastoma cell lines. They showed that Rac proteins promote the STAT3 and ERK activation and enhance cell proliferation and colony formation of glioblastoma stem-like cells. [Oncotarget] Full Article

The Interference of Notch1 Target Hes1 Affects Cell Growth, Differentiation and Invasiveness of Glioblastoma Stem Cells through Modulation of Multiple Oncogenic Targets

Scientists assessed the effects of Hes1-targeted shRNA, a Notch1 gene target, specifically on glioblastoma multiforme cancer stem cells (CSC) refractory to γ-secretase inhibitor-X. Depletion of Hes1 protein induced major changes in cell morphology, cell growth rate and in the invasive ability of shHes1-CSC in response to growth factor EGF. shHes1-CSC showed a decrease of the stemness marker Nestin concurrently to a marked increase of neuronal marker MAP2 compared to pLKO.1-CSC. [Oncotarget] Full Article

Notch3 Signaling-Mediated Melanoma–Endothelial Crosstalk Regulates Melanoma Stem-Like Cell Homeostasis and Niche Morphogenesis

Since the phenotypic characteristics and functional integrity of melanoma stem-like cells (MSLCs) depend on their vascular niche, using a two-dimensional melanoma–endothelium co-culture model, where the MSLC niche is recapitulated in vitro, researchers identified Notch3 signaling pathway as a micro-environmental cue governing MSLC phenotypic plasticity via pathway-specific gene expression arrays. [Lab Invest] Abstract

Biology and Relevance of Human Acute Myeloid Leukemia Stem Cells

The authors review studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human acute myeloid leukemia stem cells and discuss critical questions that need to be addressed in future research. [Blood] Abstract

Therapeutic Implications of Cellular and Molecular Biology of Cancer Stem Cells in Melanoma

Standard conventional oncology treatments such as chemotherapy, radiotherapy and surgical resection are only responsible for shrinking the bulk of the tumor mass and tumor tends to relapse. Thus, targeting cancer stem cells and their microenvironment niche addresses the alternative of traditional cancer therapy. [Mol Cancer] Full Article

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

NeuroVive’s New Generation of Sanglifehrin-Based Compounds Demonstrate Potent Inhibitory Effects on Human Hepatocellular Cancer Cells

NeuroVive Pharmaceutical AB presented preclinical data from a new generation of sanglifehrin-based compounds with potent inhibitory effects on hepatocellular carcinoma (HCC) cells and anti-cancer activity in an experimental model of HCC at a scientific conference. [Press release from NeuroVive Pharmaceutical AB discussing research presented at the European Association for the Study of the Liver (EASL) Hepatocellular Carcinoma (HCC) Summit, Geneva] Press Release

Prof. Thomas Gajewski Honored for Pioneering Cancer Research

The National Cancer Institute, a branch of the National Institutes of Health, has awarded an Outstanding Investigator Award to Prof. Thomas Gajewski. The award supports scientists who demonstrate remarkable productivity in cancer research and guarantees $600,000 in direct costs per year for seven years. [University of Chicago] Press Release

Takeda Presents $1 Million Gift to the Koch Institute for Integrative Cancer Research at MIT to Support Immuno-Oncology Research

Takeda Pharmaceutical Company Limited and the Koch Institute for Integrative Cancer Research at MIT jointly announced that Takeda will support groundbreaking science in immuno-oncology at the Koch Institute. Over the next two years, the $1 million gift will help to build upon the research currently being conducted by the Institute to investigate the role of the immune response in cancer and develop potential novel treatments. [Takeda Pharmaceutical Company Limited] Press Release

‘Riskiest Ideas’ Win $50 Million from Chan Zuckerberg Biohub

The biomedical research initiative created by Facebook co-founder Mark Zuckerberg and his wife, physician Priscilla Chan, has awarded its first grants to scientists, on topics ranging from the genomics of obscure microbes to a memory-retrieval device. [Nature News] Editorial

The Most Powerful Man in UK Science on His New Role

Mark Walport is preparing to take on the most powerful job in UK science. From 2018, he will be the first head of a new central funding organization called UK Research and Innovation, which will oversee more than £6 billion of research funding per year. [Nature News] Editorial

NEW Stem Cell Summit
April 26-28, 2017
Boston, United States

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

NEW Postdoctoral Research Fellow Positions – Biomedical Research (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Fellow – Cancer Stem Cells (Boston Children’s Hospital/Harvard Medical School)

Principal Investigator – Cancer Research and Oncology Drug Discovery (Southern Research Institute)

Research Fellow – Cancer and Stem Cell Biology (National University of Singapore)

Research Associate/Assistant – Leukemia and Stem Cell Biology (King’s College London)

Principal Scientist – Oncology (Janssen)

Postdoctoral Research – Cancer Genetics and Epigenetics (Fred Hutchinson Cancer Research Center)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Viruses and Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer and Developmental Biology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cell Cycle Control and Tumorigenesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Ubiquitin System and Cancer (Fred Hutchinson Cancer Research Center)

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