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Cell interactions leading to tumorigenesis: Role of senescent cells
Intercellular Dialogue and Interactome: Pathological Implications
Research Centre or Institution : Centro de Biología Molecular Severo Ochoa. CSIC - UAM
Abstract
Senescent cells represent a class of animal cells that acquire a set of unique features in response to physiological or chemical stresses. They stop dividing and suffer a number of major metabolic changes that make them different from surrounding cells. A very relevant feature is the acquisition of the Senescence Associated Secretory Phenotype (SASP): they secrete diverse types of signals, which are integrated by neighbor non-senescent cells. Some of these signals behave as growth factors and induce overproliferation of the non-senescent cells, what often causes tumorous overgrowths.
The principal goal of this project is to study the interactions between senescent and non-senescent cells that reside within the same tissue and especially those responsible for the overgrowth of the tissue. We have recently developed a simple and reliable method to generate senescent cells in the fruitfly Drosophila and propose to make use of the sophisticated genetic technology of Drosophila to study those interactions. We have identified the Jun N-Terminal Kinase (JNK) transduction pathway as the key factor in the transformation of a normal cell towards senescence, and have also found JNK-dependent proliferative signals emanating from senescent cells. We plan to analyze the function of JNK in regions, the wing appendage, in which interactions between senescent and non-senescent cells give rise to tumor formation, and in regions like the thorax in which those interactions are not tumorigenic. We will carry out ATAC-seq screens and single-cell sequencing experiments in the wing and thorax to detect and subsequently characterize JNK target genes that are differentially expressed in those regions and may be associated with tumorigenic processes
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