Cancer Stem Cell News Volume 8.06 | Feb 20 2019

TOP STORY

Adaptive Endoplasmic Reticulum Stress Signaling via IRE1α-XBP1 Preserves Self-Renewal of Hematopoietic and Pre-Leukemic Stem Cells

The authors report that the adaptive signaling of the unfolded protein response, IRE1α-XBP1, protected hematopoietic stem cells (HSCs) from endoplasmic reticulum stress-induced apoptosis. IRE1α knockout led to reduced reconstitution of HSCs. [Nat Cell Biol] Abstract

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ORP4L Extracts and Presents PIP₂ from Plasma Membrane for PLCβ3 Catalysis: Targeting It Eradicates Leukemia Stem Cells

Researchers developed an inhibitor, LYZ-81, which targeted ORP4L with high affinity and specificity and selectively eradicated leukemia stem cells (LCSs) in vitro and in vivo. ORP4L was expressed in LSCs but not in normal hematopoietic stem cells and was essential for LSC bioenergetics and survival. [Cell Rep] Full Article | Graphical Abstract

CXCL11 Promotes Self-Renewal and Tumorigenicity of α2δ1⁺ Liver Tumor-Initiating Cells through CXCL11/CXCR3/ERK1/2 Signaling

Investigators found that the expression of an inflammation-related molecule C-X-C motif chemokine 11 (CXCL11) was significantly upregulated in α2δ1⁺ hepatocellular carcinoma tumor-initiating cells and that CXCL11 induced the expression of stem cell-related genes, such as BMI1, NANOG, MDR1, ABCG2, and CACNA2D1. [Cancer Lett] Abstract

Soft Fibrin Matrix Downregulates DAB2IP to Promote Nanog-Dependent Growth of Colon Tumor-Repopulating Cells

Researchers used salmon fibrin gel to provide a 3D extracellular matrix for colon cancer cells and investigated its effects on cell growth as well as the underlying mechanisms. [Cell Death Dis] Full Article

BAG3 Deletion Suppresses Stem Cell-Like Features of Pancreatic Ductal Adenocarcinoma via Translational Suppression of ISG15

Scientists revealed that BAG3 did not interact with IFN-stimulated genes 15 (ISG15), but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer. It was further found that BAG3 deletion stabilized ISG15 mRNAs, while suppressed its translation via increasing serine phosphorylation of Ago2 at position 387. [Biochim Biophys Acta Mol Cell Res] Abstract

An FBXW7-ZEB2 Axis Links EMT and Tumor Microenvironment to Promote Colorectal Cancer Stem Cells and Chemoresistance

Investigators identified a key molecular pathway that was responsible for the formation of drug-resistant CSC populations. Using a modified yeast-2-hybrid system and 2D gel-based proteomics methods, they showed that the E3-ubiquitin ligase FBXW7 directly bound and degraded the epithelial-mesenchymal transition (EMT)-inducing transcription factor ZEB2 in a phosphorylation-dependent manner. [Oncogenesis] Full Article

Nr5a2 Promotes Cancer Stem Cell Properties and Tumorigenesis in Nonsmall Cell Lung Cancer by Regulating Nanog

Using a LLC-SD model, through transient and stable siRNA interference of Nr5a2 expression, the authors provided convincing evidence for a regulatory role of Nr5a2 in the maintenance of lung CSC self‐renewal and stem cell properties in vitro. [Cancer Med] Full Article

Direct Interactions With Cancer-Associated Fibroblasts Lead to Enhanced Pancreatic Cancer Stem Cell Function

Cancer-associated fibroblasts enhanced pancreatic ductal adenocarcinoma clonogenic growth, self-renewal, and migration that was associated with an increase in the frequency of CSCs. [Pancreas] Abstract

Chromatin Remodeler HELLS Maintains Glioma Stem Cells through E2F3 and MYC

Interrogating in silico glioma databases for epigenetic regulators that correlate with cell cycle regulation, researchers identified the chromatin remodeler, HELLS, as a potential target in glioblastoma. Glioblastoma stem cells preferentially expressed HELLS compared to their differentiated tumor progeny and non-malignant brain cells. [JCI Insight] Abstract | Full Article

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Current Approaches in Identification and Isolation of Cancer Stem Cells

The authors summarize current techniques for effective isolation and characterization of CSCs with a focus on advantages and limitations of each method with clinical applications. [J Cell Physiol] Abstract

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Xencor Announces Partial Clinical Hold on Phase I Study of XmAb14045

Xencor, Inc. announced that the FDA has placed a partial clinical hold on its Phase I study of XmAb14045, a CD123 x CD3 bispecific antibody molecule being evaluated in patients with relapsed or refractory acute myeloid leukemia and other CD123-expressing hematologic malignancies. [Xencor, Inc.] Press Release

ADC Therapeutics Announces First Patient Dosed in Phase I Clinical Trial of ADCT-402 (Loncastuximab Tesirine) and Ibrutinib in Patients with Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

ADC Therapeutics announced that the first patient has been dosed in a Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-402 in combination with Pharmacyclics LLC’s ibrutinib in patients with advanced diffuse large B-cell lymphoma or mantle cell lymphoma. [ADC Therapeutics] Press Release

Facebook’s Controversies Now Extend to Health and Medicine Issues

The Facebook controversies have come to the world of health and medicine. After last year’s scandals involving Cambridge Analytica and Russian trolls, this time the controversies concern anti-vaccine information and health privacy. [STAT News] Editorial

Trump Science Adviser Calls for More Collaboration Between Industry and Government

Kelvin Droegemeier, newly minted science adviser to US President Donald Trump, wants industry to take a larger role in funding research, with the ultimate goal of ushering in a “second golden era” of US science. [Nature News] Editorial

NEW Keystone Symposia: Cancer Stem Cells – Advances in Biology and Clinical Translation
October 13-17, 2019
Hong Kong, China

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NEW Tenure Track Faculty Position – Cancer Biology & Therapeutics (Geisel School of Medicine at Dartmouth)

Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

Postdoctoral Positions – Stem Cell and Cancer Biology (Columbia University Irving Medical Center)

Tenure Track Faculty Position – Cancer Biology & Therapeutics (Geisel School of Medicine at Dartmouth)

Postdoctoral Position – Ovarian Cancer Stem Cells (University of Minnesota)

Postdoctoral Position – Stem Cell Aging and Cancer (University of California – San Francisco)

Postdoctoral Fellow – Epigenetics and Cancer (The University of Texas MD Anderson Cancer Center)

Postdoctoral Position – Stem Cells, Development and Cancer (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Associate – Pediatrics, Cancer Biology (University of Massachusetts)

Postdoctoral Position – Colon Cancer (Vanderbilt University)

Assistant Professor – Cancer Biology (University of Pennsylvania Perelman School of Medicine)

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