Ewing sarcoma (ES) is a highly aggressive pediatric tumor driven by the RNA-binding protein EWS (EWS)/friend leukemia integration 1 transcription factor (FLI1) chimeric transcription factor, which is involved in epithelial-mesenchymal transition (EMT). EMT stabilizes a hybrid cell state, boosting metastatic potential and drug resistance. Nevertheless, the mechanisms underlying the maintenance of this hybrid phenotype in ES remain elusive.
View Article and Find Full Text PDFThe Wnt pathway is important to regulate a variety of biochemical functions and can contribute to cancer development through its influence on the epithelial-mesenchymal transition (EMT). Multiple circuits have been reported to participate in the regulation of the Wnt signaling, however, the way these circuits coordinately regulate this signaling is still unclear. Moreover, the mechanisms responsible for the appearance of hybrid phenotypes (cells presenting both E and M features) are not well determined.
View Article and Find Full Text PDFA recent model proposing that a barrier is raised against tumor evolution in pre-cancer tissues is investigated. For that we quantify expression alterations in genome maintenance pathways: DNA damage response, death pathways and cell cycle and also differentially expressed genes in transcriptomes of pre-cancerous and cancerous lesions deposited in the GEO database. We find that the main alterations in pre-cancer samples comprising the barrier are: (1) DNA double strand-breaks signaling and repair pathways induction, (2) upregulation of cyclin-dependent kinases, (3) p53 dependent (and independent) repair and apoptosis pathways induction and (4) replicative senescence induction early in tissue transformation.
View Article and Find Full Text PDFUnderstanding biochemical pathways is one of the biggest challenges in the field of molecular biology nowadays. Computer science can contribute in this area by providing formalisms and tools to simulate and analyse pathways. One formalism that is suited for modelling concurrent systems is Milner's Calculus of Communicating Systems (CCS).
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