Cancer Stem Cell News Volume 8.29 | Jul 31 2019

TOP STORY

NOX1-Dependent mTORC1 Activation via S100A9 Oxidation in Cancer Stem-Like Cells Leads to Colon Cancer Progression

In the spheroid-derived xenograft tumors, NOX1 was preferentially expressed in LGR5-positive cells. Dependence on NOX1 expression or mTOR kinase activity was corroborated in the xenograft tumors and mouse colon cancer-derived organoids. [Cell Rep] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

GPER-Induced Signaling Is Essential for the Survival of Breast Cancer Stem Cells

Investigators showed greater expression of G protein-coupled estrogen receptor-1 (GPER) in breast (B) CSCs than non-BCSCs of three patient-derived xenografts of ER^–/PR⁺ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. [Int J Cancer] Abstract

A Versatile Polyion Complex Can Intelligently Respond to a Tumor Microenvironment to Eliminate Tumor Stem Cells for Enhanced Lung Cancer Targeted Therapy

A versatile polyion complex was rationally designed, to respond to a tumor microenvironment and exhibit a size-variable property, which allowed it to possess remarkable tumor penetration capability and to accumulate around lung CSCs. Protein tyrosine kinase 7 antibody mediated active targetability facilitated the cellular uptake of triphenylphosphine-docetaxel and microRNA-31 and the breakage of the disulfide bond could also enhance intracellular drug release. [Biomater Sci] Abstract | Graphical Abstract

Revealing Dynamic Regulations and the Related Key Proteins of Myeloma-Initiating Cells by Integrating Experimental Data into a Systems Biological Model

Scientists developed a stiffness associated signaling pathway to describe the dynamic regulations of myeloma initiating cells (MICs), but also clearly identifed three critical proteins governing MIC proliferation and death, including FAK, mTORC1 and NFκB, which were validated to be related with multiple myeloma by their immunohistochemistry experiment, computation and manually reviewed evidence. [Bioinformatics] Abstract

Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition

Using two different identification strategies, researchers studied the overlap between metastatic stem cells and tumor-initiating cells (TICs) in the MMTV-PyMT model. Results showed that in the MMTV-PyMT model, Lin^–CD90^–ALDH^high cells retained a high tumor-initiating potential in orthotopic transplants, in contrast to Lin^–CD24⁺CD90⁺, which retained higher metastatic capacity. [Stem Cell Reports] Full Article | Graphical Abstract

Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

To confirm the central role of serine/threonine kinase 2 (AKT2), the authors silenced AKT2 expression via small interfering RNA and using a chemical inhibitor, in both CSCs and non-CSCs from different cancer cell lines. Results revealed that AKT2 inhibition effectively prevented non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSsC and CSCs. [Cancers] Abstract | Download Full Article

Defining Protein Pattern Differences among Molecular Subtypes of Diffuse Gliomas Using Mass Spectrometry

Abundance changes were compared to IDH-matched glioblastoma stem-like cells (GSCs) to better pinpoint protein patterns enriched in putative cellular drivers of gliomas. Using this integrative approach, scientists outlined specific proteins involved in chloride transport and epithelial-to-mesenchymal transition that showed concordant IDH-status dependant abundance differences in both primary tissue and purified GSC cultures. [Mol Cell Proteomics] Abstract

Inhibition of Breast Cancer Growth via miR-7 Suppressing ALDH1A3 Activity Concomitant with Decreasing Breast Cancer Stem Cell Subpopulation

Researchers found that aldehyde dehydrogenases-positive cells were higher in CD44⁺CD24^– and CD44⁺CD24^–ESA⁺BCSCs than that in both BT549 and MDA‐MB‐231 cell lines but microRNA‐7 level was lower in CD44⁺CD24^– and CD44⁺CD24^–ESA⁺breast cancer CSCs than that in MDA-MB-231 cells. [J Cell Physiol] Full Article

A Multiple Breast Cancer Stem Cell Model to Predict Recurrence of T_1-3, N₀ Breast Cancer

Investigators developed a prognostic model to predict recurrence based on the prevalence of breast cancer stem cells in breast cancer. Immunohistochemistry and dual-immunohistochemistry were performed to quantify the stem cells of the breast cancer patients. [BMC Cancer] Full Article

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The Emerging, Multifaceted Role of Mitophagy in Cancer and Cancer Therapeutics

The authors shed some light on the role of mitophagy in stemness and differentiation during the transition of cells’ fate, which could have a crucial role in cancer progression and metastasis. They deal with the detailed molecular mechanisms underlying mitophagy, along with highlighting the dual role of mitophagy in different aspects of cancer, suggesting it as a possible target in the mitophagy-modulated cancer therapy. [Semin Cancer Biol] Abstract

Ursodeoxycholic Acid and Cancer: From Chemoprevention to Chemotherapy

Investigators review the anticancer properties of ursodeoxycholic acid (UDCA) and synthetic antitumor derivatives designed over the past 20 years. Paradoxically, depending on the conditions, UDCA exhibits both pro- and anti-apoptotic properties toward different cell types. [Pharmacol Ther] Abstract

RhoC: A Fascinating Journey from a Cytoskeletal Organizer to a Cancer Stem Cell Therapeutic Target

Observations suggest that Ras homolog gene family member C (RhoC) imparts the plasticity required by tumor cells to exhibit such diverse functions based on microenvironmental cues. This was further confirmed by recent reports which show that it regulates cancer stem cells in breast, ovary and head and neck cancers. [J Exp Clin Cancer Res] Full Article

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Oncotelic’s Patented Lead Anti-Cancer Drug Candidate as Well as Drug Delivery Platform for Brain Tumors on Track for Advanced Pivotal Phase III Clinical Testing

Oncotelic Inc. announced that its team members will participate and provide clinical development updates at upcoming medical-scientific conferences regarding the clinical development plans for the portfolio drugs OT101 and OXi4503 aimed at their regulatory approval. [Oncotelic Inc. (GlobeNewswire, Inc.)] Press Release

VBI Vaccines Announces Dosing of First Recurrent GBM Patient in Part B of Ongoing Phase I/IIa Study of VBI-1901

VBI Vaccines Inc. announced that the first patient has been dosed in Part B of the ongoing Phase I/IIa clinical study of VBI-1901, VBI’s oncology immunotherapeutic, in recurrent glioblastoma (GBM) patients. [VBI Vaccines Inc.] Press Release

SELLAS Advances Galinpepimut-S (GPS) in Combination with KEYTRUDA^® (Pembrolizumab) Program with Dosing of First Patient in Phase 1/2 Basket Study

SELLAS Life Sciences Group, Inc. announced the dosing of the first patient in its Phase I/II open-label study of GPS in combination with Merck’s anti-PD-1 therapy KEYTRUDA^®, in patients with selected WT1-positive advanced cancers, including both solid tumors and hematologic malignances. [SELLAS Life Sciences Group, Inc.] Press Release

NIH Announces Details of Human Fetal Tissue Research Restrictions

On July 26, the National Institutes of Health announced new restrictions on human fetal tissue research for scientists applying for grants using the material from elective abortions. Starting in September, scientists writing grants for experiments that involve this type of fetal tissue will be required to explain why other tissue types can’t be used and where the researchers plan to get the tissue. [The Scientist] Editorial

China’s Scientists Alarmed, Bewildered by Growing Anti-Chinese Sentiment in the United States

Scientists in China are concerned about what they see as growing anti-Chinese sentiment in the United States. They dismiss claims of a vast conspiracy to steal US intellectual property and worry that new visa restrictions, scrutiny of export of scientific devices, and US investigations of Chinese and Chinese American scientists will hinder international collaborations. That could harm both countries’ research efforts as well as global scientific progress, many say. [ScienceInsider] Editorial

Japan Approves First Human-Animal Embryo Experiments

A Japanese stem-cell scientist is the first to receive government support to create animal embryos that contain human cells and transplant them into surrogate animals since a ban on the practice was overturned earlier this year. Hiromitsu Nakauchi, who leads teams at the University of Tokyo and Stanford University in California, plans to grow human cells in mouse and rat embryos and then transplant those embryos into surrogate animals. [Nature News] Editorial

NEW European Cancer (ECCO) Summit 2019
September 12-14, 2019
Brussels, Belgium

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

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

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

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Postdoctoral Research Position – B-Cell Acute Lymphoblastic Leukemia Research (University of California San Francisco)

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)

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