Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021
Erindi/veggspjald / Talk/poster E81
Höfundar / Authors: Kevin Ostacolo (1), Margrét Helga Ögmundsdóttir (2)
Starfsvettvangur / Affiliations: Faculty of Medicine
Kynnir / Presenter: Kevin Ostacolo
Autophagy is a highly conserved cellular function that allows the recycling of damaged macromolecules and organelles. Autophagy starts with the formation, the elongation, and the maturation of a double membrane phagophore. The final step is the fusion with a lysosome resulting in an autolysosome in which degradation occurs. Autophagy plays a dual role in the carcinogenic process, inhibiting the initiation process, while promoting tumor growth, metastasis and therapeutic resistance during tumor progression. The autophagy related gene ATG7 is involved in autophagy initiation by facilitating the lipidation of LC3 at the phagophore. Moreover, Atg7 deletion has been shown to be important for tumor growth in pancreatic adenocarcinoma mouse model. Recently, our team identified an isoform of ATG7 (ATG7(2)) that cannot lipidate LC3. In this study we found that ATG7(2) is linked with malignancy in human pancreatic adenocarcinoma. Indeed, patients with low expression of ATG7(2) have a 50% of survival at 30 months while patients with high expression have only 25% survival. Our analyses point towards a mechanism by which the hippo and TGF-β signaling pathways are involved. These pathways are known to lead to oncogenesis and chemotherapeutic resistance when deregulated. It will be important to further dissect out the mechanisms by which ATG7 is involved in oncogenesis in pancreatic adenocarcinoma.