210B Poster - 01. Cell Stress and cell death
Friday April 08, 2:00 PM - 4:00 PM

Non-apoptotic activation of Drosophila Caspase-2/9 limits the growth of open-wound-like tumours by modulating JNK signalling and the tumour microenvironment


Authors:
Luis Alberto Lopez 1; Derek Xu 1; Kenneth Yamada 2

Affiliations:
1) University of Oxford; 2) National Institute of Dental and Craniofacial Research, NIH.

Keywords:
a. caspases; h. tumorigenesis

Personalised cancer therapy requires a deep molecular understanding of tumour features and the interplay between transformed cells and the immunological microenvironment. We have capitalized on a clinically relevant Drosophila tumour model, which simultaneously upregulates the EGFR and JAK/STAT signalling pathways (EJS tumours), to investigate the role of caspases in regulating tumour properties. Our results indicate that widespread non-apoptotic activation of initiator caspases limits JNK signalling and ensures cell fate commitment in EJS tumours. Additionally, caspase activation lowers the remote recruitment and in situ proliferation of EJS tumour-associated macrophages that fuel tumour growth. These findings uncover unrecognised tumour-suppressor activities of caspases that prevent exacerbation of cellular malignancy and tumour overgrowth without inducing apoptosis. Furthermore, they encourage the exploration of caspase-based therapeutic approaches against EGFR/JAK-STAT-activating tumours.