Intestinal Cell News 3.28 July 28, 2017 | |
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TOP STORYInvestigators applied a strategy to induced pluripotent stem cells derived from patients with familial adenomatous polyposis harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and they generated colonic organoids that exhibited enhanced WNT activity and increased epithelial cell proliferation, which they used as a platform for drug testing. [Nat Med] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)INTESTINAL CANCERS & DISEASESPeptidomimetic Inhibitors of APC–Asef Interaction Block Colorectal Cancer Migration The authors rationally designed a series of peptidomimetics that act as potent inhibitors of the adenomatous polyposis coli (APC) interface. By using the peptidomimetic inhibitor as a chemical probe, they found that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation in colorectal cancer cells. [Nat Chem Biol] Abstract Researchers found that the reduced expression of core 3 synthase correlated with metastasis to lymph nodes and distant organs, resulting in poor prognosis for colorectal cancer patients. They revealed that mucin-type core 3 O-glycan was synthesized at the membrane-tethered MUC1 N terminus because of core 3 synthase expression in colon cancer cells. [Oncogene] Abstract Intracrine VEGF Signaling Mediates Colorectal Cancer Cell Migration and Invasion Since extracellular vascular endothelial growth factor (VEGF) signaling regulates migration of endothelial cells and various tumor cells, investigators attempted to determine whether intracrine VEGF signaling affects colorectal cancer (CRC) cell motility. Depletion of intracellular VEGF and VEGF receptor 1 in multiple CRC cell lines led to strong inhibition of migration and invasion of CRC cells. [Br J Cancer] Abstract The authors established MARCH2 knockout HCT116 cell lines using CRISPR/Cas9-mediated genome editing to evaluate the role of MARCH2 in colon cancer in vitro and in vivo. Knockout of MARCH2 suppressed cell proliferation, and promoted autophagy, apoptosis and G2/M phase cell cycle arrest. [Cell Death Dis] Full Article miR-181d and c-Myc-Mediated Inhibition of CRY2 and FBXL3 Reprograms Metabolism in Colorectal Cancer Scientists demonstrated that knockdown of miR-181d suppressed colorectal cancer cell proliferation, migration, and invasion by impairing glycolysis. Mechanistically, miR-181d stabilized c-myc through directly targeting the 3′-UTRs of CRY2 and FBXL3, which subsequently increased the glucose consumption and the lactate production. [Cell Death Dis] Full Article Expression Profile of Intestinal Stem Cell Markers in Colitis-Associated Carcinogenesis The authors examined the expression profiles of markers in colitis-associated carcinogenesis to investigate whether they can be used as biomarkers for the early detection of dysplasia. Crypt base columnar stem cell markers increased continuously with tumor development, whereas a +4 cell expression profile was not present. [Sci Rep] Full Article Researchers investigated the biological and clinical role of Hox transcript antisense intergenic RNA (HOTAIR) in 5-fluorouracil (5FU) resistance in colorectal cancer (CRC). Their results showed that HOTAIR negatively regulated miR-218 expression in CRC through an EZH2-targeting miR-218-2 promoter regulatory axis. [Mol Ther Nucleic Acids] Full Article INTESTINAL STEM CELL & ORGANOID RESEARCHX-box–binding protein 1 deletion in the epithelium was shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand mouse UL16-binding protein (ULBP)–like transcript 1 and its human orthologue cytomegalovirus ULBP via endoplasmic reticulum stress–related transcription factor C/EBP homology protein. [J Exp Med] Abstract Desmoglein 2 Regulates the Intestinal Epithelial Barrier via p38 Mitogen-Activated Protein Kinase Desmoglein 2 (Dsg2), an adhesion molecule of desmosomes and the only Dsg isoform expressed in enterocytes, is required for epithelial barrier properties and may contribute to barrier defects in Crohn’s disease. Scientists identified extradesmosomal Dsg2 on the surface of polarized enterocytes by Triton extraction, confocal microscopy, SIM and STED. [Sci Rep] Full Article Enhanced Uptake of Fe3O4 Nanoparticles by Intestinal Epithelial Cells in a State of Inflammation Researchers investigated the uptake of Fe3O4 nanoparticles (NPs) by intestinal epithelial cells under inflammatory conditions via the light scattering of flow cytometry and inductively coupled plasma mass spectrometry techniques. The results of the correlation analysis indicated that the uptake ratios of Fe3O4 NPs by intestinal epithelial cells under inflammatory conditions were higher than those under the control conditions. [Molecules] Full Article | |
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REVIEWSRole of ADAM10 in Intestinal Crypt Homeostasis and Tumorigenesis The author reviews some of the proposed functions of A disintegrin and metalloproteinase (ADAM) 10 associated with intestinal crypt homeostasis and tumorigenesis within the gastrointestinal tract in vivo. [Biochim Biophys Acta] Abstract Tumor Organoids as a Pre-Clinical Cancer Model for Drug Discovery Scientists highlight what is currently known about tumor organoid culture, the advantages and challenges of the model system, compare it with other pre-clinical cancer models, and evaluate its value for drug development. [Cell Chem Biol] Abstract Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
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INDUSTRY NEWSDr. Reddy’s Laboratories Ltd. and CHD Bioscience Inc. announced a global licensing agreement for the clinical development and commercialization of Dr. Reddy’s Phase III clinical trial candidate, DFA-02. It is intended to be used for the prevention of surgical site infections, following non-emergency, elective colorectal surgery. [Dr. Reddy’s Laboratories Ltd.] Press Release Merus N.V. announced that the U.S. Court of Appeals for the Federal Circuit affirmed the trial court’s conclusion that Regeneron Pharmaceuticals, Inc. engaged in inequitable conduct before the United States Patent and Trademark Office while prosecuting U.S. Patent No. 8,502,018, entitled “Methods of Modifying Eukaryotic Cells.” [Merus N.V.] Press Release The St. Baldrick’s Foundation awarded 90 new grants totaling $23.5 million in its summer grant cycle to support the brightest minds in the pediatric cancer field. The largest grant is for $5.8 million to the Children’s Oncology Group, whose member institutions treat more than 90 percent of kids with cancer in the U.S. [The St. Baldrick’s Foundation] Press Release | |
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POLICY NEWSFirst U.S. Team to Gene-Edit Human Embryos Revealed Since Chinese researchers announced the first gene editing of a human embryo two years ago, many expected that similar work in the United States was inevitable. The MIT Technology Review broke the news that such experiments have happened. [ScienceInsider] Editorial At Harvard, Extraordinary Court Battle between Ph.D. Student and Prominent Researcher Grinds On The conflict between Gustavo German, a Harvard doctoral student in biomedicine, and Lee Rubin, a prominent stem cell researcher, has continued to evolve. Amid continued legal jousting, the situation has remained difficult for all of the parties involved in this tumultuous episode. [ScienceInsider] Editorial
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EVENTSNEW Keystone Symposia: Tumor Metabolism Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Gut Microbiota and Colon Cancer (University of Toronto) Group Leader – Host Pathogen Interactions (QIMR Berghofer Medical Research Institute) Postdoctoral Position – Intestinal Organoids (Radboud University) Postdoctoral Research Associate – Cancer Research (Southern Research Institute) Postdoctoral Position – Intestinal Epithelial Cell Biology (University of Gothenburg) Postdoctoral Research Associate – Colorectal Cancer (University of Virginia) Postdoctoral Research Fellow – Cancer Epidemiology (Fred Hutchinson Cancer Research Center) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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