Estudio del inflamasoma en células de cáncer de pulmón

Abstract

ABSTRACT : The inflammasome is a cytosolic multiprotein complex system defending the cell against external attacks or aberrations of its own. Inflammasomes are molecular platforms activating the pro inflammatory caspases (caspase-1, -4 and -5) which induce a cascading activation of different routes that ends in the activation of the interleukin-1 pathway, or the rupture of the cell membrane producing inflammatory dying by pyroptosis. This proptosis is mediated by a family of proteins called gasdermins (GSDM), where the best known is GSDMD. GSDMD is cleaved into its two units by the proinflammatory caspases, and its N-terminal fragment forms lytic pores in the cell membrane. We aim to study the inflammasome and pyroptosis as a therapeutic target in cancer. To do this, we study the expression of the components of the inflammasome and their alteration in lung cancer cells. first, we set up controls of the pathway in THP-1 cells, which are cells of the immune system known to respond to distinct inflammasome activating stimuli. Second, we assessed the expression of the components inflammasome and pyroptotic pathways caspase 1; caspase 4; IL1B; GDMD; GSDME and NINJ1 in lung cancer cell lines at protein and mRNA level. Finally, we studied if activation of cellular senescence in lung cancer cells with different drugs used in the clinic modulate the inflammasome pathway. Our overall aim is to understand the spectrum of alterations of the pathways activating inflammasomes and pyroptosis in cancer cells which could lead to the identification of a therapeutic target for the clinic.