<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "MYCN modulates the restriction point\r\nand ferroptosis in Neuroblastoma"^^ . "Neuroblastoma is the most common extracranial solid tumor in childhood. It constitutes\r\nan interesting model for tumor progression since the mutation rate is relatively low as\r\ncompared to other tumors, allowing to investigate specific tumor drivers in a relatively\r\nhomogeneous genetic background. One of the important drivers of tumor formation in\r\nneuroblastoma is the oncogene MYCN. This transcription factor is responsible for the\r\nactivation of a cascade of genes involved in cell proliferation and metabolism The study\r\nof MYCN’s role in these processes is highly relevant because a deep understanding of\r\nthe regulation could lead to more effective therapies for MYC-driven tumors. In this PhD\r\nthesis, an approach was developed to study cell cycle and metabolism on MYCN-driven\r\nneuroblastomas. One of the caveats of cell cycle studies is the lack of markers to study\r\ncell cycle transition, and the artifacts caused by cell synchronization. By combining the\r\nE2F1-d2GFP and Cdt1-degron markers it was possible to identify a G0-like state, which\r\nis more prominent upon reduction of MYCN. This state is transient and it was not\r\npossible to detect it before in this cell system. The cells under high MYCN expression\r\navoid passing through the G0-like state. This decision happens early in the cell cycle\r\nand it is not influenced by p21, contrary to what was found in other studies. Gene\r\nexpression profiling of sorted cells using the cell cycle markers demonstrated that the\r\ntranscriptional program of G0-like state caused by MYCN reduction is different from\r\nmitogen starvation and contact inhibition, suggesting that the G0-like state might be a\r\nspectrum of states with similar phenotypes but distinct expression profiles. As an\r\noutlook, the network analysis of the expression data suggests RABL6 as a potential\r\nmarker of MYCN that controls the commitment to cell cycle by inhibiting p16, however\r\nfurther experiments are required to confirm this finding. From the metabolic perspective,\r\nwe found that MYCN-high cells are strongly addicted to the amino acid cystine, which\r\nserves as a source for the glutathione pathway. Inhibition of enzymes from this pathway\r\nshows a dramatic lethal effect exclusively on MYCN-high cells. We found that the\r\nmechanism of cell death under cystine starvation in MYCN-amplified cells is ferroptosis,\r\na recently described pathway that involves lipid peroxidation enhanced by iron. To our\r\nknowledge, this is the first time that MYCN is associated with ferroptosis which opens an\r\navenue for developing new drugs targeting MYC-driven tumors via induction of\r\nferroptosis."^^ . "2017" . . . . . . . "Andrés Felipe"^^ . "Flórez Amaya"^^ . "Andrés Felipe Flórez Amaya"^^ . . . . . . "MYCN modulates the restriction point\r\nand ferroptosis in Neuroblastoma (PDF)"^^ . . . "Andres_Florez_PhD_thesis_2016.pdf"^^ . . . "MYCN modulates the restriction point\r\nand ferroptosis in Neuroblastoma (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "MYCN modulates the restriction point\r\nand ferroptosis in Neuroblastoma (Other)"^^ . . . . . . "preview.jpg"^^ . . . "MYCN modulates the restriction point\r\nand ferroptosis in Neuroblastoma (Other)"^^ . . . . . . "medium.jpg"^^ . . . "MYCN modulates the restriction point\r\nand ferroptosis in Neuroblastoma (Other)"^^ . . . . . . "small.jpg"^^ . . . "MYCN modulates the restriction point\r\nand ferroptosis in Neuroblastoma (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #22626 \n\nMYCN modulates the restriction point \nand ferroptosis in Neuroblastoma\n\n" . "text/html" . .