SFEBES2021 Poster Presentations Late Breaking (60 abstracts)
Metabolomic analysis of succinate dehydrogenase subunit knockout in phaeochromocytoma and neuroblastoma cell lines
Grace Salsbury 1 , Jordan E Read 1 , Valle Morales 2 , Charlotte L Hall 1 , Eugénie S Lim 1 , Scott A Akker 1 , Katiuscia Bianchi 2 & Paul Chapple 1
1William Harvey Research Institute, Queen Mary University of London, London, United Kingdom;2Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
Loss of function of succinate dehydrogenase (SDH), caused by mutations in each of the 4 subunits – SDHA/B/C and D – is associated with development of phaeochromocytomas and paragangliomas (PPGLs). The mutations lead to loss of enzymatic activity and subsequent accumulation of the oncometabolite succinate, a driver of tumourigenesis. It is well established but poorly understood why mutations in SDHB are associated with more aggressive metastatic disease than the other SDH subunits. Moreover, it is not known why these SDH-deficient tumours arise predominantly from chromaffin cells as opposed to other cell types. Using CRISPR/Cas9, we have generated knockouts of subunits A and B in both the rat phaeochromocytoma-derived PC-12 chromaffin cell line and the human SH-SY5Y neuroblastoma neural crest cell line. We have subsequently used a mass spectrometry-based metabolomics approach to compare the metabolite profiles of the knockouts in both the phaeochromocytoma and neuroblastoma cell lines. This analysis has identified metabolite profiles that are unique to the chromaffin knockout cell models, potentially identifying metabolic vulnerabilities that are specific to PPGLs and could be targeted in the treatment of these tumours.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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