Short-term activation of the Jun-N terminal Kinase pathway in apoptosis-deficient cells of Drosophila induces tumorigenesis
Speaker: Noelia Pinal Seoane
Centro de Biología Molecular "Severo Ochoa" (CBMSO) de Madrid
Host: Pedro Lazo
Salón de Actos del Centro de Investigación del Cáncer
In Drosophila the Jun-N terminal Kinase (JNK) pathway has a principal pro-apoptotic function aimed to eliminate aberrant cells that appear after stress or after oncogenic transformations. It also performs other non-apoptotic functions associated with morphogenesis and cell proliferation but experimental analysis of the latter is hindered by its pro-apoptotic activity. Here we report the response of apoptosis-deficient cells to short–term JNK induction, achieved by ionising irradiation, by pulses of P53, or of JNK activity itself. We show that any of those events causes high irrepressible levels of JNK activity, associated with high ROS levels, which persist for the rest of the development. As a consequence, there is continuous function of pathways downstream JNK like JAK/STAT, Wg and Dpp, what results in large tumour-like overgrowths. We also show that the oncogenic potential of the overexpression of the Ras-MAPK pathway resides largely on its ability to suppress apoptosis. It has been proposed that a hallmark of tumour cells is that they can evade apoptosis. In reverse, we propose that in Drosophila cells refractory to apoptosis become tumorigenic due to their property of acquiring persistent JNK activity after stress events that are inconsequential in tissues in which cells are open to apoptosis.