2020
DOI: 10.1186/s13046-020-01681-0
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Lysine-222 succinylation reduces lysosomal degradation of lactate dehydrogenase a and is increased in gastric cancer

Abstract: Background: Lysine succinylation is an emerging posttranslational modification that has garnered increased attention recently, but its role in gastric cancer (GC) remains underexplored. Methods: Proteomic quantification of lysine succinylation was performed in human GC tissues and adjacent normal tissues by mass spectrometry. The mRNA and protein levels of lactate dehydrogenase A (LDHA) in GC and adjacent normal tissues were analyzed by qRT-PCR and western blot, respectively. The expression of K222-succinylate… Show more

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Cited by 81 publications
(56 citation statements)
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“…Moreover, the mRNA and protein levels of LDHA were positively associated with H19 levels in GC cells. Importantly, LDHA was highly expressed in GC samples, 35,36 and involved in glucose metabolism, proliferation, and migration of GC cells. 37,38 Therefore, we inferred that H19 par- knockdown decreased PDK1 expression through the let-7/HIF-1α axis in hypoxia, and ablation of PDK1 counteracted H19-mediated glycolysis, suggesting that H19 modulated glycolysis through the let-7/HIF-1α/PDK1 axis.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, the mRNA and protein levels of LDHA were positively associated with H19 levels in GC cells. Importantly, LDHA was highly expressed in GC samples, 35,36 and involved in glucose metabolism, proliferation, and migration of GC cells. 37,38 Therefore, we inferred that H19 par- knockdown decreased PDK1 expression through the let-7/HIF-1α axis in hypoxia, and ablation of PDK1 counteracted H19-mediated glycolysis, suggesting that H19 modulated glycolysis through the let-7/HIF-1α/PDK1 axis.…”
Section: Discussionmentioning
confidence: 99%
“…For instance, stability of tumor suppressor p53 is increased by acetylation counteracting ubiquitylation ( Caron et al, 2005 ) and direct acetylation of ubiquitin is an inhibitor of polyubiquitylation ( Ohtake et al, 2015 ). Very recently, the inhibition of ubiquitylation by succinylation was demonstrated for lactate dehydrogenase resulting in higher cell proliferation, invasion, and migration in gastric cancer ( Li et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%
“…The stability of succinylated LDHA was maintained to promote cell growth and invasion by reducing the degradation of ubiquitinated LDHA. 226 Glutamine (Gln) can be converted to α- Ketoglutarate enters the tricarboxylic acid (TCA) cycle and plays a key role in synthesizing intermediates of mitochondrial metabolism, maintaining tumor cell growth, and signal regulation. 227 The two glutaminase isoforms are liver-type (GLS2) and kidney-type (GLS), in which the site 311 of GLS is activated by succinylation to resist oxidative stress and promote tumor survival by increasing glutamine decomposition and NADPH/glutathione production.…”
Section: The Biological Effect Of Ptms On Tumor Cells In Tmementioning
confidence: 99%