Cancer Stem Cell News Volume 8.36 | Sep 18 2019

TOP STORY

KLF4 Represses DYRK2 Inhibition of Self-Renewal and Survival through c-Myc and p53 in Leukemia Stem/Progenitor Cells

Mechanistically, KLF4 repressed the Dyrk2 gene in leukemic stem/progenitor cells; thus, loss of KLF4 resulted in elevated levels of DYRK2 kinase, which were associated with inhibition of survival and self-renewal via depletion of c-Myc protein and p53 activation. In addition to transcriptional regulation, stabilization of DYRK2 protein by inhibiting ubiquitin E3 ligase SIAH2 with vitamin K3 promoted apoptosis and abrogated self-renewal in murine and human chronic myeloid leukemia stem/progenitor cells. [Blood] Abstract

(Ranked by impact factor of the journal)

The JAK2/STAT3/CCND2 Axis Promotes Colorectal Cancer Stem Cell Persistence and Radioresistance

By investigating public databases containing colorectal cancer (CRC) patient data, researchers explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts. [J Exp Clin Cancer Res] Full Article

circPTN Sponges miR-145-5p/miR-330-5p to Promote Proliferation and Stemness in Glioma

Real-time PCR was used to examine the expression of circPTN in glioma tissues and normal brain tissues. Assays of dual- luciferase reporter system, biotin label RNA pull-down and FISH were used to determine that circPTN could sponge miR-145-5p and miR-330-5p. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell. [J Exp Clin Cancer Res] Full Article

Aberrations in Notch-Hedgehog Signalling Reveal Cancer Stem Cells Harboring Conserved Oncogenic Properties Associated with Hypoxia and Immunoevasion

Employing a comparative approach involving 21 cancers, investigators uncovered clinically-relevant, pan-cancer drivers of Notch and Hedgehog. GISTIC datasets were used to evaluate copy number alterations. Receiver operating characteristic and Cox regression were employed for survival analyses. [Br J Cancer] Abstract

Expression of Oncogenic Drivers in 3D Cell Culture Depends on Nuclear ATP Synthesis by NUDT5

Comparison of 2D versus 3D cancer cell cultures from different tissues of origin suggest that NUDT5 increases the aggressiveness of the disease via the modulation of several key driver genes, including ubiquitin specific peptidase 22, RAB35B, focadhesin and prostagladin E synthase. NUDT5 functioned as a master regulator of key oncogenic pathways and of genes involved in cell adhesion, cancer stem cell maintenance and epithelial to mesenchyme transition. [Cancers] Abstract

DNA-Methylation-Mediated Silencing of miR-7-5p Promotes Gastric Cancer Stem Cell Invasion via Increasing Smo and Hes1

The stem cell marker CD44 was used to sort gastric (G) CSCs by fluorescence‐activated cell sorting. They found that CD44 (+) cells had higher invasiveness and formed more number of sphere colonies than CD44 (−) cells. Quantitative real-time PCR revealed that the miR-7-5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine-deprived medium. [J Cell Physiol] Abstract

An Anticancer Os(II) Bathophenanthroline Complex as a Human Breast Cancer Stem Cell-Selective, Mammosphere Potent Agent That Kills Cells by Necroptosis

The authors showed that Os(II) complex 2 was capable of efficient and selective killing CSCs in heterogeneous populations of human breast cancer cells MCF-7 and SKBR-3. Notably, its submicromolar potency to kill CSCs was considerably higher than that of its Ru analog, [Ru(η6-pcym)(bphen)(dca)]PF6, and salinomycin, one of the most selective CSC-targeting compounds hitherto identified. [Sci Rep] Full Article

miR-133b Suppresses Colorectal Cancer Cell Stemness and Chemoresistance by Targeting Methyltransferase DOT1L

Researchers report that miR-133b was downregulated in colorectal spheroids, which were enriched with CSC and displayed stem cell-like characteristics, including upreulation of CSCs surface markers and elevated chemoresistance. Additionally, miR-133b overexpression reduced colorectal cancer (CRC) stemness and overrode chemoresistance to 5-Fluorouracil and oxaliplatin, indicating a negative role of miR-133b in regulating CRC stemness and chemoresistance. [Exp Cell Res] Abstract

Differentially Expressed microRNAs in MIA PaCa-2 and PANC-1 Pancreas Ductal Adenocarcinoma Cell Lines Are Involved in Cancer Stem Cell Regulation

Scientists report the miRNA expression characteristics of two cell lines, MIA PaCa-2 and PANC-1, and discovered three miRNAs that were involved in CSC suppression. After transfection of each miRNA’s mimic into PANC-1 cells which exhibited higher stemness feature than MIA-PaCa-2 cells, partial reduction of CSC surface markers and inhibition of tumor sphere formation were observed. [Int J Mol Sci] Full Article

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Cancer Stem Cells and Their Unique Role in Metastatic Spread

The authors highlight the role of CSCs in every step of the metastatic cascade from cancer cell invasion into blood vessels, survival in the blood stream, attachment and extravasation as well as colonization of the host organ and subsequent establishment of distant macrometastasis. [Semin Cancer Biol] Abstract

Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness

Investigators survey the latest evidence concerning the role of genomic alteration in current triple-negative breast cancer (TNBC) treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. [Cancers] Full Article

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Bristol-Myers Squibb Provides Update on Phase III Opdivo (Nivolumab) CheckMate -548 Trial in Patients with Newly Diagnosed MGMT-Methylated Glioblastoma Multiforme

Bristol-Myers Squibb Company announced that the Phase III CheckMate -548 trial evaluating the addition of Opdivo to the current standard of care versus the standard of care alone did not meet one of its primary endpoints, progression-free survival, in patients with newly diagnosed glioblastoma multiforme that is O6-methylguanine-DNA methyltransferase (MGMT)-methylated. [Bristol-Myers Squibb Company] Press Release

Genmab Announces Positive Topline Results in Phase III Study of Daratumumab in Combination with Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma

Genmab A/S annoucned topline results from the Phase III CANDOR study, sponsored by Amgen, of daratumumab in combination with carfilzomib and dexamethasone (Kd) versus Kd alone in patients with multiple myeloma who have relapsed after one to three prior therapies. The study met the primary endpoint of improving progression free survival. [Genmab A/S] Press Release

Kura Oncology Doses First Patient in Phase I Clinical Trial of Menin-MLL Inhibitor KO-539 in Acute Myeloid Leukemia

Kura Oncology, Inc. announced that the first patient has been dosed in a Phase I clinical trial of KO-539, the company’s first-in-class inhibitor of the menin-mixed lineage leukemia (menin-MLL) interaction, in patients with relapsed or refractory acute myeloid leukemia. [Kura Oncology, Inc.] Press Release

GT Biopharma Announces FDA Notification of Commencement of Enrollment in Human GTB-3550 Trike™ Phase I/II Clinical Trial

GT Biopharma, Inc. announced that it notified the FDA that it was commencing enrollment in its first-in-human GTB-3550 Phase I/II clinical trial. [GT Biopharma, Inc.] Press Release

Celgene Announces Phase III QUAZAR^® AML-001 Study of CC-486 as Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Met Primary and Key Secondary Endpoints

Celgene Corporation announced top-line results from the international Phase III, randomized, double-blind, placebo-controlled study, QUAZAR AML-001. The study evaluated the efficacy and safety of investigational therapy CC-486 as maintenance therapy in patients with newly diagnosed acute myeloid leukemia (AML) who achieved first complete response or complete response with incomplete blood count recovery with induction chemotherapy. [Celgene Corporation] Press Release

Senate Bill Would Give NIH $3 Billion in 2020, or 7.7% Boost

A Senate spending panel today released a draft 2020 spending bill containing a hefty $3 billion increase for the National Institutes of Health (NIH) that would bring the agency’s total budget to $42.1 billion. That 7.7% boost is $1 billion more than a House of Representatives committee approved in its version of the bill in April, and would amount to a 40% increase in NIH’s budget over the past 5 years. [ScienceMagazine] Editorial

New Deals Could Help Scientific Societies Survive Open Access

A project that included funders backing Plan S, the European-led effort to speed the transition to open access, released a set of contract templates and tips meant to help small, independent publishers reach deals with libraries that would eventually eliminate subscriptions while protecting revenue. [ScienceInsider] Editorial

Trump’s Top Scientist Outlines Plan to Reduce Foreign Influence on US Research

After months of outcry over whether the United States government is unfairly targeting foreign-born researchers over purported security breaches, President Donald Trump’s science adviser is launching an effort to strengthen national policies on research security. [Nature News] Editorial

NEW Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges
January 19-23, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Researcher – Cancer (Max Planck Institute for Molecular Genetics)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Associate Professor – T-Cell Therapy (Dana-Farber Cancer Institute)

Postdoctoral Researcher – Stem Cells and Cancer (IRB Barcelona)

Postdoctoral Fellow – Cancer Progression (NIH/NCI – Center for Cancer Research)

Associate Professor – Immunology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Scientist – Cancer and Leukemia (St. Jude Children’s Research Hospital)

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

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

Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

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