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ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells

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Genes & Diseases 2020年第4期7卷 620-635页

作者： Luca Tirinato Francesca Pagliari Simone Di Franco Elisa Sogne Maria Grazia Marafioti jeanette jansen Andrea Falqui Matilde Todaro Patrizio Candeloro Carlo Liberale Joao Seco Giorgio Stassi Enzo Di Fabrizio Biomedical Physics in Radiation Oncology DKFZ(German Cancer Research Center)69120 HeidelbergGermany Physical Science and Engineering(PSE)Division King Abdullah University of Science and Technology(KAUST)ThuwalSaudi Arabia Department of Experimental and Clinical Medicine University“Magna Graecia”of Catanzaro88100 Loc.GermanetoCatanzaroItaly Biological and Environmental Sciences and Engineering(BESE)Division King Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia Cellular and Molecular Pathophysiology Laboratory Department of SurgicalOncological and Stomatological SciencesUniversity of PalermoPalermoItaly Ruprecht Karls University Heidelberg Department of Physics69120 HeidelbergGermany Department of Health Promotion Mother and Child CareInternal Medicine and Medical Specialties(PROMISE)University of PalermoPalermoItaly

Lipid Droplets(LDs)are emerging as crucial players in colon cancer development and *** expression has been associated with high tumorigenicity in Cancer Stem Cells(CSCs),so that they have been proposed as a new functional marker in Colorectal Cancer Stem Cells(CR-CSCs).They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory *** is growing evidence that a possible connection between metabolic alterations and malignant transformation exists,although the effects of nutrients,primarily glucose,on the CSC behavior are still mostly *** is an essential fuel for cancer cells,and the connections with LDs in the healthy and CSC populations merit to be more deeply ***,we showed that a high glucose concentration activated the PI3K/AKT pathway and increased the expression of CD133 and CD44v6 CSC ***,glucose was responsible for the increased amount of Reactive Oxygen Species(ROS)and LDs in both healthy and CR-CSC *** also investigated the gene modulations following the HG treatment and found out that the healthy cell gene profile was the most ***,Atorvastatin,a lipidlowering drug,induced the highest mortality on CR-CSCs without affecting the healthy counterpart.

关键词： Cholesterol metabolism Colorectal cancer stem cells Fatty acid

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