Short-term activation of the Jun N-terminal kinase pathway in apoptosis-deficient cells of Drosophila induces tumorigenesis.

In Drosophila, the JNK pathway eliminates by apoptosis aberrant cells that appear in development. It also performs other functions associated with cell proliferation, but analysis of the latter is hindered by the pro-apoptotic activity. We report the response of apoptosis-deficient cells to transient activation of JNK and show that it causes persistent JNK function during the rest of the development. As a consequence, there is continuous activity of the downstream pathways JAK/STAT, Wg and Dpp, which results in tumour overgrowths. We also show that the oncogenic potential 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, apoptosis-deficient cells 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.