The multifaceted roles of sulfane sulfur species in cancer-associated processes

Zuhra, Karim; Tomé, Catarina S.; Forte, Elena; Vicente, João B.; Giuffrè, Alessandro

doi:10.1016/j.bbabio.2020.148338

Cited by 22 publications

(26 citation statements)

References 200 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have indicated that H 2 S, acknowledged to be an important gasotransmitter, is involved in cancer biological processes. 5,6 H 2 S is produced in mammalian cells by three major enzymes including cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and MPST. 7 Numerous studies have shown altered expression of these enzymes in the progression of various types of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

3‐Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma

Song

Jin

et al. 2022

Liver International

View full text Add to dashboard Cite

Background and Aims:The prognosis of hepatocellular carcinoma (HCC) remains dismal, and its molecular pathogenesis has not been completely defined. The enzyme 3-mercaptopyruvate sulfurtransferase (MPST) regulates endogenous hydrogen sulfide (H 2 S) biosynthesis. However, the role of MPST in HCC has never been intensively investigated.Methods: MPST protein expression was analysed in HCC tumour tissues and matched adjacent tissues. The effect of MPST on HCC progression was studied in vitro and in vivo. Results: The mRNA and protein expression of MPST was significantly downregulated in HCC samples compared with their paired nontumour counterparts. A low MPST expression was associated with larger tumour size and a worse overall survival. Overexpression of MPST in HCC cells inhibited cell proliferation and induced apoptosis. MPST overexpression also significantly suppressed the growth of tumour xenografts in nude mice, whereas silencing MPST by intratumour delivery of siRNA substantially promoted tumour growth. Moreover, diethylnitrosamine-induced mouse HCC was aggravated by MPST gene knockout. Mechanistically, MPST suppressed the cell cycle associated with H 2 S production and inhibition of the AKT/FOXO3a/ Rb signalling pathway in HCC development. In addition, MPST expression negatively correlated with that of pRb in HCC specimens and the combination of these two parameters is a more powerful predictor of poor prognosis. Conclusions: MPST may function as a tumour suppressor gene that plays an essential role in HCC proliferation and liver tumorigenesis. It is a candidate predictor of clinical outcome in patients with HCC and may be used as a biomarker and intervention target for new therapeutic strategies.

show abstract

Section: Introductionmentioning

confidence: 99%

3‐Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma

Song

Jin

et al. 2022

Liver International

View full text Add to dashboard Cite

show abstract

“…Interestingly, several proteins pertaining to migration, including the focal protein kinase encoded by PTKN2, have also been found to undergo persulfidation in HeLa cells treated with EGF, a known pro-migratory signaling factor (Zivanovic et al 2019). Most of these increases in protein persulfidation are presumably mediated by CBS and/or CSE activity, as supported by studies implementing inactivation of these enzymes and/or by their conspicuous expression in the biological systems under scrutiny (Mustafa et al 2009) (Gao et al 2015) (Untereiner et al 2017) (Zivanovic et al 2019) (Zuhra et al 2021). MPST-mediated protein persulfidation has so far been reported for only two proteins, the sulfurtransferase Mocs3 and thioredoxin (Trx).…”

Section: Discussionmentioning

confidence: 95%

“…Whether the advantage conferred by this post-translational modification stems from a mere overall protection of proteins from hyperoxidative damage or from more specific consequences remains to be determined. The few surveys of persulfidated proteins performed without exogenous dihydrogene sulfide (H 2 S) supply showed that persulfidation affected proteins involved notably in energetic pathways (Ida et al 2014) (Gao et al 2015) and migration and associated signaling pathways (Zivanovic et al 2019) (Murphy et al 2019) (Zuhra et al 2021). For instance, proteins of the glycolysis pathway were reported to be persulfidated in a human pancreatic beta cell line (Gao et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Human glioblastoma cell motility depends on the activity of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase

Saurty-Seerunghen

Daubon

Bellenger

et al. 2022

Preprint

View full text Add to dashboard Cite

Cancer cells in similar functional states are found in all glioblastoma, despite the genomic heterogeneity observed between and within these brain tumors. Metabolism being downstream of all signaling pathways regulating cell behaviors, we looked for metabolic weaknesses in link with motility, a key functional state for glioblastoma aggressiveness. A signature-driven data reduction approach highlighted motile cells present in thirty tumors from four independent single-cell transcriptomic datasets. Analyses integrating trajectory modeling disclosed, as characteristic of motile cells, enhanced oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). The soundness of this prediction was verified using migration and invasion assays with patient-derived cells and tissue organoids. Pharmacological and genetic manipulations showed that enhanced ROS production and MPST activity are required for glioblastoma cell motility. Biochemical assays indicated that MPST acts by protecting protein cysteine residues from dismal hyperoxidation. In vivo, MPST knockdown translated in reduced tumor burden, and a robust increase in mice survival. These results show that enhanced oxidative stress coupled with MPST mobilization plays a key role in glioblastoma cell motility.

show abstract

“…The proliferation- and expansion-resistant cancer type can be stopped by induction and sensitization to oxidative stress [ 217 ]. In response to the generation of reactive oxygen/nitrogen/sulfur species (ROS/RNS/RSS), the protein cysteine thiols (R–SH) undergo a range of oxidative modifications, for example: nitrosylation (R–SNO), sulfenylation (R–SOH), and persulfidation (S-sulfuration, R–SSH) [ 218 , 219 ]. The enzymes that possess catalytic cysteine residues of the active site are exposed to a constant attack by hydrogen peroxide [ 189 ].…”

Section: Sulfurtransferasesmentioning

confidence: 99%

Sulfur Administration in Fe–S Cluster Homeostasis

2021

View full text Add to dashboard Cite

Mitochondria are the key organelles of Fe–S cluster synthesis. They contain the enzyme cysteine desulfurase, a scaffold protein, iron and electron donors, and specific chaperons all required for the formation of Fe–S clusters. The newly formed cluster can be utilized by mitochondrial Fe–S protein synthesis or undergo further transformation. Mitochondrial Fe–S cluster biogenesis components are required in the cytosolic iron–sulfur cluster assembly machinery for cytosolic and nuclear cluster supplies. Clusters that are the key components of Fe–S proteins are vulnerable and prone to degradation whenever exposed to oxidative stress. However, once degraded, the Fe–S cluster can be resynthesized or repaired. It has been proposed that sulfurtransferases, rhodanese, and 3-mercaptopyruvate sulfurtransferase, responsible for sulfur transfer from donor to nucleophilic acceptor, are involved in the Fe–S cluster formation, maturation, or reconstitution. In the present paper, we attempt to sum up our knowledge on the involvement of sulfurtransferases not only in sulfur administration but also in the Fe–S cluster formation in mammals and yeasts, and on reconstitution-damaged cluster or restoration of enzyme’s attenuated activity.

show abstract

The multifaceted roles of sulfane sulfur species in cancer-associated processes

Cited by 22 publications

References 200 publications

3‐Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma

3‐Mercaptopyruvate sulfurtransferase represses tumour progression and predicts prognosis in hepatocellular carcinoma

Human glioblastoma cell motility depends on the activity of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase

Sulfur Administration in Fe–S Cluster Homeostasis

Contact Info

Product

Resources

About