Cancer Stem Cell News Volume 6.14 | Apr 12 2017

TOP STORY

A Stemness-Related ZEB1-MSRB3 Axis Governs Cellular Pliancy and Breast Cancer Genome Stability

Scientists showed that the differentiation status of normal human mammary epithelial cells dictates cell behavior after an oncogenic event and predetermines the genetic routes toward malignancy. Whereas oncogene induction in differentiated cells induced massive DNA damage, mammary stem cells were resistant, owing to a preemptive program driven by the transcription factor ZEB1 and the methionine sulfoxide reductase MSRB3. [Nat Med] Abstract

(Ranked by impact factor of the journal)

Clinical Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating Tumor Cells of Men with Metastatic Castration-Resistant Prostate Cancer Treated with First- and Second-Line Abiraterone and Enzalutamide

The authors reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer. Here, they expanded their cohort size to better characterize the prognostic significance of AR-V7 in this setting. [J Clin Oncol] Full Article

CHK1-Targeted Therapy to Deplete DNA Replication-Stressed, p53-Deficient, Hyperdiploid Colorectal Cancer Stem Cells

There are limited therapeutic options for advanced colorectal cancer, particularly for tumors carrying RAS-activating mutations. Scientists aimed to identify novel cancer stem cell (CSC)-targeting strategies. The drug-library screening led to the identification of LY2606368 as a potent anti-CSC agent acting in vitro and in vivo in tumor cells from a considerable number of patients. [Gut] Full Article

A Novel AHI-1-BCR-ABL-DNM2 Complex Regulates Leukemic Properties of Primitive Cml Cells through Enhanced Cellular Endocytosis and ROS-Mediated Autophagy

Researchers demonstrated that the scaffold protein AHI-1 is highly deregulated in leukemic stem cells (LSCs) and interacts with multiple proteins, including dynamin-2 (DNM2), to mediate tyrosine kinase inhibitor-resistance of LSCs. They demonstrated that the SH3 domain of AHI-1 and the proline rich domain of DNM2 are mainly responsible for this interaction. [Leukemia] Abstract

Monocytic and Granulocytic Myeloid Derived Suppressor Cells Differentially Regulate Spatiotemporal Tumor Plasticity during Metastatic Cascade

Investigators demonstrated that monocytic (mMDSC) and granulocytic subsets of myeloid-derived suppressor cells infiltrate in the primary tumor and distant organs with different time kinetics and regulate spatiotemporal tumor plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, they provided evidence that tumor-infiltrated mMDSCs facilitate tumor cell dissemination from the primary site by inducing EMT/CSC phenotype. [Nat Commun] Full Article | Press Release

ΔNp63α Promotes Adhesion of Metastatic Prostate Cancer Cells to the Bone through Regulation of CD82

ΔNp63α is a critical mediator of epithelial development and stem cell function in a variety of tissues including the skin and breast, while overexpression of ΔNp63α acts as an oncogene to drive tumor formation and cancer stem cell properties in squamous cell carcinoma. The authors discovered that ΔNp63α favors adhesion and stem-like growth of these cells in the bone microenvironment. [Oncogene] Full Article

NSPc1 Promotes Cancer Stem Cell Self-Renewal by Repressing the Synthesis of All-Trans Retinoic Acid via Targeting RDH16 in Malignant Glioma

Scientists found that nervous system polycomb 1 (NSPc1) was highly expressed in stem cell-like glioma cells (SLCs). Knockdown of NSPc1 in SLCs resulted in impaired neurosphere formation and self-renewal abilities, down-regulated expression of stemness markers such as NESTIN, CD133 and SOX2, and decreased capacity to propagate subcutaneous xenografts. [Oncogene] Abstract

Targeting KDM1A Attenuates Wnt/β-Catenin Signaling Pathway to Eliminate Sorafenib-Resistant Stem-Like Cells in Hepatocellular Carcinoma

Researchers report that the activity of lysine-specific histone demethylase 1A (KDM1A) is required for the emergence of cancer stem cells following prolonged sorafenib treatment. As such, KDM1A inhibitors, such as pargyline and GSK2879552, dramatically suppressed stem-like properties of sorafenib-resistant hepatocellular carcinoma cells. [Cancer Lett] Abstract

Systems Approach to Characterize the Metabolism of Liver Cancer Stem Cells Expressing CD133

The authors systematically analyzed and compared the global metabolic phenotype between liver cancer stem cells (LCSCs) and non-LCSCs using transcriptome and metabolome data. They demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. [Sci Rep] Full Article

Dual Inhibiting OCT4 and AKT Potently Suppresses the Propagation of Human Cancer Cells

AKT serves as an epigenetic modulator that links epigenetic regulation to cell survival and proliferation while the epigenetic mediator OCT4 critically controls stem cell pluripotency and self-renewal. Emerging evidence indicated their complicated interplays in cancer cells and cancer stem cells, and inhibiting either one may activate the other. Researchers proposed a strategy to targeting both factors simultaneously. [Sci Rep] Full Article

The miR-200b-ZEB1 Circuit Regulates Diverse Stemness of Human Hepatocellular Carcinoma

Researchers report that the miR-200b-ZEB1 circuit is closely involved with the induction and maintenance of a diverse group of cancer stem cells. They found that miR-200b downregulation occurred in early hepatocellular carcinoma and associated with poor prognosis. [Mol Carcinog] Abstract

EMT, CSCs, and Drug Resistance: The Mechanistic Link and Clinical Implications

The authors summarize the current understanding of the link between the epithelial-to-mesenchymal transition (EMT) program and the cancer stem cell (CSC) state, and also discuss how this knowledge can contribute to improvements in clinical practice. [Nat Rev Clin Oncol] Abstract

The Evolving Concept of Cancer Stem-Like Cells in Thyroid Cancer and Other Solid Tumors

Scientists examine cancer stem-like cells (CSCs) and the relationship between epithelial to mesenchymal transition (EMT) and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. [Lab Invest] Full Article

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Organogenesis Shares Successes and Best Practices for Cell-Based Product Manufacturing

Stem cell scientists, researchers and product developers learned more about Organogenesis’ state-of-the art manufacturing process and successful commercial-scale production of FDA-approved wound healing therapies. The conference highlighted cutting-edge developments in all areas of stem cell research, including the biology, medicine, applications and regulation of stem cells. [Press release from Organogenesis Inc. discussing research presented at the 6^th Stem Cell Product Development and Commercialization Conference, Boston] Press Release

OncoMed’s Phase II Demcizumab Pancreatic Cancer Trial Misses Primary Endpoint

OncoMed Pharmaceuticals, Inc. reported top-line results from the company’s Phase II YOSEMITE clinical trial of demcizumab in combination with Abraxane^® plus gemcitabine in previously untreated patients with metastatic pancreatic cancer. The trial did not meet the primary endpoint of progression-free survival. [OncoMed Pharmaceuticals, Inc.] Press Release

Regen BioPharma, Inc. Sees Success in Its Pre-Clinical Small Molecule Optimization Program for NR2F6

Regen BioPharma Inc. has completed the first phase of its small molecule optimization program, which involved synthesizing more than 40 analogues of its initial lead compounds. The compounds synthesized consist of activators and inhibitors of NR2F6 and were identified using Regen’s patented screening methodology and unique chemical libraries. The NR2F6 nuclear receptor has been identified as a potentially very important immune cell inhibitor and cancer stem cell differentiator. [Regen BioPharma Inc. (PR Newswire Association LLC.)] Press Release

Review of Canadian Science Calls for Better Oversight, Coordination — and More Money

To reinvigorate its science base, Canada needs to “reinvest” almost CAD$500 million in basic, investigator-led research over the next four years, according to a long-awaited review of the country’s science and innovation landscape. [ScienceInsider] Editorial

U.S. Report Calls for Research Integrity Board

The U.S. research community needs to do a better job of both investigating misconduct allegations and promoting ethical conduct—or the government might act unilaterally in ways that scientists won’t like. That’s the implicit message sent by a new report out from the National Academies of Science, Engineering, and Medicine entitled Fostering Integrity in Research. [ScienceInsider] Editorial

Critics Worry Faster FDA Drug Reviews Could Compromise Safety

For biotechs, waiting for new drugs to be approved is not as hard as it used to be. Since late last year, federal regulators have acted months earlier than expected to OK a bumper crop of new drugs from Massachusetts companies. The speedy decisions are welcomed by businesses that have made massive investments in developing experimental medicines and are eager for them to start generating revenue. But critics say the Food and Drug Administration (FDA)’s hurry-up mode may sacrifice patient safety — accelerating under pressure not only from the industry and investors, but from a regulation-averse Trump administration. [Boston Globe Media Partners, LLC] Editorial

NEW Regulation and Function of Small GTPases
June 11-16, 2017
West Palm Beach, United States

NEW Protein Aggregation in Health and Disease
June 11-16, 2017
Steamboat Springs, United States

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NEW Postdoctoral Fellows – Cancer Biology (University of Texas Medical School at Houston)

Postdoctoral Positions – Epigenetics, Stem Cells and Cancer (University of Copenhagen)

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Postdoctoral Fellow – Cancer Research (Houston Methodist Research Institute)

Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine)

Postdoctoral Position – Cancer/Normal Stem Cells (Johns Hopkins University)

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