|Cancer Stem Cell News 5.47 November 30, 2016|
Some tumors undergo epithelial to mesenchymal transition (EMT) while others do not, which may reflect intrinsic properties of their cell of origin. By targeting the same oncogenic mutations to discrete skin compartments, scientists showed that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. [Cell Stem Cell]
The authors found that resistance to treatment and metastasis was attributed to expansion of stem-like tumor-initiating cells. Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. [J Exp Med]
It has been shown that lysine demethylase KDM1A is overexpressed in glioblastoma. Researchers determined whether KDM1A modulates glioma stem cells (GSCs) stemness and differentiation and tested the utility of two novel KDM1A-specific inhibitors to promote differentiation and apoptosis of GSCs. [Oncogene]
Scientists demonstrated that a microRNA—miR-383—is frequently downregulated in prostate cancer, has a critical role in determining tumor-initiating potential and is involved in prostate cancer metastasis via direct regulation of CD44, a ubiquitous marker of prostate cancer tumor-initiating cells/stem cells. [Oncogene]
Researchers found that the acidic osteosarcoma (OS) microenvironment was a key factor for mesenchymal stem cell activation, and it in turn promoted the secretion of paracrine factors that influence tumor behavior. An increased expression of IL6 and IL8 were found only in normal stromal cells, but not in OS cells, and this was confirmed in tumor-associated stromal cells isolated from OS tissue. [Int J Cancer]
Investigators showed that long non-coding RNA lncARSR was upregulated in primary renal tumor-initiating cells (T-ICs) and was associated with a poor prognosis of clear cell renal cell carcinomas. Knockdown of lncARSR attenuated the self-renewal, tumorigenicity and metastasis of renal T-ICs. [Sci Rep]
The authors found that breast cancer stem cells (CSCs) overexpressed components of the Nuclear factor-kappa B (NF-κB) signaling cascade and consequently displayed high NF-κB activity levels. Breast cancer cell lines with high proportion of CSCs exhibited high NF-κB-inducing kinase (NIK) expression. The effect of NIK in the CSC properties was assessed by mammosphere formation, mice xenografts and stem markers expression. [Sci Rep]
Redox status is known to be a critical factor in the maintenance of cancer stem cells (CSCs), and the antioxidant enzyme peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Researchers investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. [Oncotarget]
The chemically related molecules benztropine mesylate and deptropine citrate were selected for by scientists and both potently inhibited sphere formation and self-renewal of breast cancer stem cells in vitro. Benztropine mesylate treatment decreased cell subpopulations with high ALDH activity and with a CD44+/CD24– phenotype. In vivo, benztropine mesylate inhibited tumor-initiating potential. [Oncotarget]
Elevated expression of TLX in neuroblastoma (NB) has been shown to correlate with unfavorable prognosis, and TLX is required for self-renewal of NB cells. Investigators found that ASK1 phosphorylated and stabilized TLX, which led induction of HIF-1α, and its downstream VEGF-A in an Akt dependent manner. There was a novel pro-survival role of ASK1 in the tumorigenic NB cell populations. [Cell Signal]
The authors demonstrated that Wnt/β-catenin and ALDH1A1 form a signal circuit and that NOR1 antagonizes the tumor stem cell-like phenotype in nasopharyngeal carcinoma (NPC) cell lines: the ectopic overexpression of NOR1 reduced β-catenin and ALDH1A1 expression; β-catenin/TCF4 targeted the regulation of ALDH1A1 transcription in NPC cells; silencing ALDH1A1 reduced AKT and GSK-3β expression; and eventually feedback decreased β-catenin expression levels. [J Cell Physiol]
The Notch-1 pathway is crucially important to gastric cancer stem/progenitor cells (GCSPCs) and is regulated by DLL4. DLL4 and Nestin levels were measured by researchers in 383 gastric cancer tissue samples by immunohistochemistry, and the clinico-pathological features of patients assessed. DLL4 affected GCSPC stemness, altering their pathological behavior. DLL4 silencing inhibited GCSPC metastatic potential both in vitro and in vivo by impeding Notch-1 signaling pathway activation. [Cancer Med]
Scientists investigated pancreatic cancer stem cell-associated aptamers as a novel tool for diagnosis and therapeutic agents. Aptamers that bind to stemness-enriched cancer cells in pancreatic cancer were developed by modified Cell-SELEX method. [J Mol Recognit]
The authors focus on general themes shared among p53’s functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche. They also examine p53 gain of function roles in stemness. They conclude with therapeutic strategies that restore wild-type p53 function in cancer and CSCs, including RING finger E3 ligases and CSC maintenance. [Int J Mol Sci]
Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.
Chugai Pharmaceutical Co., Ltd. and Berlin-Chemie Menarini, a company of the Menarini Group, announced that both companies have entered into a global license agreement for PA799, class I PI3K inhibitor. PA799 is the PI3K inhibitor originated by Chugai, which conducted Phase I study for solid tumors in Europe. [The Menarini Group]
The Allen Institute for Cell Science has released the Allen Cell Collection: the first publicly available collection of gene edited, fluorescently tagged human induced pluripotent stem cells that target key cellular structures with unprecedented clarity. Distributed through the Coriell Institute for Medical Research, these powerful tools are a crucial first step toward visualizing the dynamic organization of cells to better understand what makes human cells healthy and what goes wrong in disease. [Allen Institute]
Could stem cells help the body recover from septic shock, heart attack and liver transplantation? Researchers from The Ottawa Hospital and the University of Ottawa are now in a better position to answer these questions, thanks to $2.2 million in peer-reviewed awards from the Stem Cell Network. The funding will support three clinical trials, representing half of the trials funded in this national competition and nearly a quarter of the overall funds awarded. [University of Ottawa]
Orchard Therapeutics Limited and researchers from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles, led by Orchard Scientific Advisory Board member Dr. Donald Kohn have been awarded $20 million by the California Institute for Regenerative Medicine’s governing board. [Orchard Therapeutics Limited]
ARIAD Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration has granted Iclusig® full approval for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor therapy is indicated; and for the treatment of adult patients with T315I-positive CML or T315I positive Ph+ ALL. [ARIAD Pharmaceuticals, Inc.]
Easing the regulatory burden on U.S. academic research certainly isn’t as sexy as curing cancer or understanding how the brain works. But creating an advisory body focused on eliminating government red tape—a tiny provision in a 996-page bill to accelerate medical research that could become law next month—is no less important to maintaining the health of the research community than is the infusion of billions of dollars, higher education lobbyists say. [ScienceInsider]
The United Kingdom may soon become the first country to explicitly permit the birth of children from embryos modified to contain three people’s DNA. At the same time, new research backs up concerns that such a treatment — which aims to erase diseases transmitted by the DNA found in cellular structures called mitochondria — may not always be 100% effective. [Nature News]
Republican congressman Tom Price of Georgia is US President-elect Donald Trump’s pick to head the US Department of Health and Human Services. If he is confirmed by the Senate, Price would oversee the National Institutes of Health, the Centers for Disease Control and Prevention and the Food and Drug Administration. [Nature News]
As US president-elect Donald Trump begins to sketch out the priorities of his administration, Nature tracks the key issues and likely leaders of vital science and research agencies. [Nature News]
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