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Studies of tumorigenesis in Drosophila: possible clinical implications

17th national competition for scientific and technical research

Metabolism and cancer

Senior Researcher : Ginés Morata Pérez

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Research Centre or Institution : Centro de Biología Molecular "Severo Ochoa". CSIC-Universidad Autónoma de Madrid


The fundamental aim of this project is to use the vinegar fly Drosophila to study the initial processes in tumour formation, as these are not normally accessible for experimental analysis in mammals. Clones of oncogenic cells will be generated for this in the imaginal discs of Drosophila. These cells will be mutant for genes that are also associated with human tumours.

Special attention will be paid to the role of cell competition, a mechanism which is conserved in insects and mammals that functions as a tumour suppressor due to its capacity to induce apoptosis in tumour cells by activation of the Jun-N-terminal Kinase (JNK) signalling pathway. Nevertheless, recent studies have shown that the anti-tumoral function of cellular competition /JNK may be reversed if the initial group of tumour cells achieves a certain size. Under these circumstances the proliferative signals generated by JNK activity in apoptotic cells stimulate the growth of the tumour. This suggests that pro-apoptotic treatments used in cancer patients may be counter-productive.

The first aim of the proposed experiments is to study the phenomenon of apoptosis in general as a tumoral stimulant under a variety of oncogenic conditions. Secondly, as the pro-apoptotic functions of cellular competition are mediated by the JNK pathway, experiments will have the objective of analysing the conditions under which it behaves as an inhibitor or stimulator of tumoral progression. Finally, we will try to identify the target genes of the JNK pathway involved in the process.

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