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Title

Dissecting the mechanisms of Notch/Akt-induced tumorigenesis: the role of energetic stress and metabolic reprogramming

AuthorsGarcía, Lucía; Nahuel Villegas, Santiago; Domínguez, María
Issue Date2019
Citation26th European Drosophila Research Conferences (2019)
AbstractThe simultaneous aberrant activation of Notch and PI3K/Pten/Akt signaling pathways generates massive tumors in flies and is also causative of several aggressive forms of human cancers such as T-cell lymphoblastic leukaemia. However, the mechanism behind this oncogenic cooperation is poorly understood. Here, we used Drosophila to investigate molecular aspects of this interaction using a model entailing the simultaneous over-activation of both Notch and Akt signaling pathways (N+Akt+) in the developing fly eye. By employing phospho-proteomic analysis on N+Akt+ induced tumors we have identified a specific downstream target belonging to the mitochondrial electron transport chain (ETC). Genetic inactivation of ETC components induces the generation of reactive oxygen species (ROS), which in turn cooperates with Notch signal to fuel tumorigenesis. We investigated the role of stress-activated JNK signaling pathway and sima/HIF1α transcriptional factor in response to high ROS levels. Interestingly, N+Akt+ tumors are JNK independent, but rely on HIF1α, the most important driver of glycolytic phenotype in cancer. Furthermore, we found that N+Akt+ combination provokes an interorgan glycolytic reprogramming that may underlie tumor growth.
DescriptionTrabajo presentado a la 26th European Drosophila Research Conferences (EDRC), celebrada en Lausanne (Switzerland) del 5 al 8 de septiembre de 2019.
URIhttp://hdl.handle.net/10261/218202
Appears in Collections:(IN) Comunicaciones congresos
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