CYCLIC AMP EXTRUSION ABROGATION INHIBITS PANC-1 CELL PROLIFERATION THROUGH ACTIVATION OF EPAC/RAP1 PATHWAY

DI SIERVI, N; SHAYO, C; ATTORRESI, A; YANEFF, A; GOMEZ, N; CAROZZO, A; DAVIO, C

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2016

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer with a 5-year survival rate of 4%. This is caused by its high resistance to conventional therapies, its delayed diagnosis and high metastatic potential. PDACs usually present high expression of Gαs and PKA phosphorylated substrates, suggesting a deregulation of the cAMP pathway, agent involved in growth and cell differentiation. Previously, we established a correlation between MRP4 expression and the level of differentiation, malignancy and cAMP extrusion capacity of PDAC cells, thus proposing it as a possible target for this disease. Our working hypothesis is that the anti-proliferative effects of MRP4 inhibition are a consequence of the modulation of cAMP extrusion. This work concentrates in unraveling which cAMP pathways are leading this process.