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Open Access 01-12-2021 | Helminths

Model systems in SDHx-related pheochromocytoma/paraganglioma

Authors: Krisztina Takács-Vellai, Zsolt Farkas, Fanni Ősz, Gordon W. Stewart

Published in: Cancer and Metastasis Reviews | Issue 4/2021

Abstract

Pheochromocytoma (PHEO) and paraganglioma (PGL) (together PPGL) are tumors with poor outcomes that arise from neuroendocrine cells in the adrenal gland, and sympathetic and parasympathetic ganglia outside the adrenal gland, respectively. Many follow germline mutations in genes coding for subunits of succinate dehydrogenase (SDH), a tetrameric enzyme in the tricarboxylic acid (TCA) cycle that both converts succinate to fumarate and participates in electron transport. Germline SDH subunit B (SDHB) mutations have a high metastatic potential. Herein, we review the spectrum of model organisms that have contributed hugely to our understanding of SDH dysfunction. In Saccharomyces cerevisiae (yeast), succinate accumulation inhibits alpha-ketoglutarate-dependent dioxygenase enzymes leading to DNA demethylation. In the worm Caenorhabditis elegans, mutated SDH creates developmental abnormalities, metabolic rewiring, an energy deficit and oxygen hypersensitivity (the latter is also found in Drosophila melanogaster). In the zebrafish Danio rerio, sdhb mutants display a shorter lifespan with defective energy metabolism. Recently, SDHB-deficient pheochromocytoma has been cultivated in xenografts and has generated cell lines, which can be traced back to a heterozygous SDHB-deficient rat. We propose that a combination of such models can be efficiently and effectively used in both pathophysiological studies and drug-screening projects in order to find novel strategies in PPGL treatment.

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Title: Model systems in SDHx-related pheochromocytoma/paraganglioma
Authors: Krisztina Takács-Vellai
Zsolt Farkas
Fanni Ősz
Gordon W. Stewart
Publication date: 01-12-2021
Publisher: Springer US
Keyword: Helminths
Published in: Cancer and Metastasis Reviews / Issue 4/2021
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-021-10009-z

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