Cancer Stem Cell News Volume 6.10 | Mar 15 2017

TOP STORY

Targeting BMI1⁺ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma

Investigators showed through lineage tracing and genetic ablation that BMI1⁺ cancer stem cells (CSCs) mediate invasive growth and cervical lymph node metastasis in a mouse model of squamous cell carcinoma in the head and neck (HNSCC). This model and primary human HNSCC samples contain highly tumorigenic, invasive, and cisplatin-resistant BMI1⁺ CSCs, which exhibit increased AP-1 activity that drives invasive growth and metastasis of HNSCC. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Antagonism of EGFR and Notch Limits Resistance to EGFR Inhibitors and Radiation by Decreasing Tumor-Initiating Cell Frequency

Scientists showed that dual targeting of epidermal growth factor receptor (EGFR) and Notch2/3 receptors with antibody CT16 not only inhibited signaling mediated by these receptors but also showed a strong anti–stem cell effect both in vitro and in vivo. [Sci Transl Med] Abstract | Press Release

Inhibition of Serotonin Receptor Type 1 in Acute Myeloid Leukemia Impairs Leukemia Stem Cell Functionality: A Promising Novel Therapeutic Target

Acute myeloid leukemia (AML) cells differentially expressed serotonin receptor type 1 (HTR1) compared with healthy blood cells and the most primitive hematopoietic fraction; HTR1B expression on AML patient samples correlated with clinical outcome. Inhibition of HTR1s activated the apoptosis program, induced differentiation and reduced the clonogenic capacity, while minimal effect was observed on healthy blood cells. [Leukemia] Abstract

ER–Mitochondria Contacts Control Surface Glycan Expression and Sensitivity to Killer Lymphocytes in Glioma Stem‐Like Cells

The authors found that the mitochondrial morphology of glioma stem‐like cells (GSCs) modulates the ER–mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER–mitochondria contacts compared to glioma differentiated cells. [EMBO J] Abstract | Graphical Abstract

Oncostatin M Promotes Cancer Cell Plasticity through Cooperative STAT3-SMAD3 Signaling

While it is clear that the tumor microenvironment (TME) contributes to cancer cell plasticity, the specific TME factors most actively controlling plasticity remain largely unknown. Researchers performed a screen to identify TME cytokines and growth factors that promote epithelial–mesenchymal plasticity, and acquisition of cancer stem cell properties. [Oncogene] Full Article

CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). Scientists reported that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95^high-expressing glioblastoma neurospheres. [Cell Rep] Full Article | Graphical Abstract

Stem Cell Factors-Based Identification and Functional Properties of In Vitro-Selected Subpopulations of Malignant Mesothelioma Cells

Cancer stem cells-enriched malignant mesothelioma cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1) increased resistance to cisplatin, (2) increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3) a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models. [Stem Cell Reports] Full Article | Graphical Abstract

A Core Regulatory Circuit in Glioblastoma Stem Cells Links MAPK Activation to a Transcriptional Program of Neural Stem Cell Identity

To investigate common regulatory networks in both neural and glioblastoma stem cells, researchers subjected both cell types to in vitro differentiation conditions and measured global gene-expression changes using gene expression microarrays. [Sci Rep] Full Article

Treating Triple Negative Breast Cancer Cells with Erlotinib plus a Select Antioxidant Overcomes Drug Resistance by Targeting Cancer Cell Heterogeneity

Treatment with CAT-SKL—a re-engineered protein form of the antioxidant enzyme catalase—inhibited cancer stem-like cells (CSCs), and treatment with the EGFR-specific small molecule kinase inhibitor erlotinib inhibited non-CSCs. Combining the antioxidant CAT-SKL with erlotinib targeted both CSCs and bulk cancer cells in cultures of EGFR-expressing triple-negative breast cancer-derived cells. The authors also report evidence that the mechanism for CAT-SKL inhibition of CSCs may depend on antioxidant-induced downregulation of a short alternative mRNA splicing variant of the methyl-CpG binding domain 2 gene, isoform MBD2c. [Sci Rep] Full Article

FAM83A Is Amplified and Promotes Cancer Stem Cell-Like Traits and Chemoresistance in Pancreatic Cancer

Investigators found family with sequence similarity 83, member A (FAM83A) is significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, cancer stem cells-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. [Oncogenesis] Full Article

Notch Signaling Plays a Crucial Role in Cancer Stem-Like Cells Maintaining Stemness and Mediating Chemotaxis in Renal Cell Carcinoma

Scientists aimed to explore the effect of Notch pathway on stemness of cancer stem cells in renal cell carcinoma and the underlying mechanisms. [J Exp Clin Cancer Res] Full Article

Emerging Drugs Targeting Epithelial Cancer Stem-Like Cells

The authors review drugs targeting cancer stem-like cells, in selected epithelial cell-derived cancers. [Stem Cells] Full Article

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

Boston Biomedical to Present Preclinical Data on Targeting Cancer Stemness at AACR 2017

Boston Biomedical will present data from six preclinical studies – including five late-breaking posters – from its research and development portfolio. [Press release from Boston Biomedical discussing research to be presented at 2017 American Association for Cancer Research (AACR) Annual Meeting, Washington D.C.] Press Release

FDA Approves Merck’s KEYTRUDA^® (Pembrolizumab) for Adult and Pediatric Patients with Classical Hodgkin Lymphoma (cHL) Refractory to Treatment, or who Have Relapsed after Three or More Prior Lines of Therapy

Merck announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA^®, the company’s anti-programmed death receptor-1 therapy, for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after three or more prior lines of therapy. [Merck] Press Release

Novartis Kisqali^® (Ribociclib, LEE011) Receives FDA Approval as First-Line Treatment for HR⁺/HER2^– Metastatic Breast Cancer in Combination with Any Aromatase Inhibitor

The US Food and Drug Administration (FDA) has approved Kisqali^® in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR⁺/HER2) advanced or metastatic breast cancer. [Novartis] Press Release

‘Zombie’ Patent Fights over Mutant Mice Return

Like a zombie that keeps on kicking, legal battles over mutant mice used for Alzheimer’s research are haunting the field once again — four years after the last round of lawsuits. In the latest case, the University of South Florida in Tampa has sued the US National Institutes of Health for authorizing the distribution of a particular type of mouse used in the field. [Nature News] Editorial

U.K. Scientists Prepare for Impending Break with European Union

For months after the United Kingdom (U.K.) voted last June to leave the European Union (EU), many British scientists clung to hopes of a “soft Brexit,” which would not cut them off from EU funding and collaborators. But Prime Minister Theresa May, who is expected to trigger the two-year process of exiting the European Union, has signaled the break will be sharp. U.K. researchers are now facing up to the prospect that they won’t be able to apply for EU funding or easily recruit students and colleagues from the rest of Europe. [ScienceInsider] Editorial

Canada’s New Genetic Privacy Law Is Causing Huge Headaches for Justin Trudeau

A vote in Canada’s Parliament to approve a genetic privacy bill is creating a self-inflicted political headache for Prime Minister Justin Trudeau’s Liberal government—and could result in a relatively rare and unusual court case. [ScienceInsider] Editorial

Physician with Drug-Industry Ties Is Trump’s FDA Pick

President Donald Trump has nominated Scott Gottlieb — a conservative pundit, physician and venture capitalist — to head the US Food and Drug Administration (FDA). [Nature News] Editorial

NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
May 11-13, 2017
Heidelberg, Germany

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