Role of 3-mercaptopyruvate Sulfurtransferase in Cancer: Molecular Mechanisms and Therapeutic Perspectives

Overview

Journal Transl Oncol

Date 2025 Jan 15

PMID 39813769

Authors

Ka Zhang

Yi-Wen Zhu

Ao-Qi Tang

Ze-Tao Zhou

Yi-Lun Yang

Zi-Hui Liu

Yan Li

Xiao-Yi Liang

Zhi-Fen Feng

Jun Wang

Tong Jiang

Qi-Ying Jiang

Dong-Dong Wu

Affiliations

Soon will be listed here.

Abstract

The occurrence and development of tumor is mediated by a wide range of complex mechanisms. Subsequent to nitric oxide and carbon monoxide, hydrogen sulfide (HS) holds the distinction of being the third identified gasotransmitter. Alternation of HS level has been widely demonstrated to induce an array of disturbances in important cancer cell signaling pathways. As a result, the effects of HS-catalyzing enzymes in cancers also attract widspread attention. 3-mercaptopyruvate sulfurtransferase (3-MST) is privileged to be one of them. In fact, 3-MST is overexpressed in many tumors including human colon cancer, lung adenocarcinoma, and bladder urothelial carcinoma. But it is also lowly expressed in hepatocellular carcinoma. In this review, we focus on the generation of endogenous HS and polysulfides, facilitated by 3-MST. Additionally, we delve deeply into the potential role of 3-MST in tumorigenesis and development. The impact of 3-MST inhibition on the development of tumors and its potential for tumor therapy are also highlighted.

References

Uhl E, Wolff F, Mangal S, Dube H, Zanin E . Light-Controlled Cell-Cycle Arrest and Apoptosis. Angew Chem Int Ed Engl. 2020; 60(3):1187-1196. PMC: 7839536. DOI: 10.1002/anie.202008267. View

Li Q, Qu M, Wang N, Wang L, Fan G, Yang C . Betaine protects rats against ischemia/reperfusion injury-induced brain damage. J Neurophysiol. 2022; 127(2):444-451. DOI: 10.1152/jn.00400.2021. View

Ascencao K, Dilek N, Zuhra K, Modis K, Sato T, Szabo C . Sequential Accumulation of 'Driver' Pathway Mutations Induces the Upregulation of Hydrogen-Sulfide-Producing Enzymes in Human Colonic Epithelial Cell Organoids. Antioxidants (Basel). 2022; 11(9). PMC: 9495861. DOI: 10.3390/antiox11091823. View

Fiorucci S, Antonelli E, Mencarelli A, Orlandi S, Renga B, Rizzo G . The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis. Hepatology. 2005; 42(3):539-48. DOI: 10.1002/hep.20817. View

Pedre B, Dick T . 3-Mercaptopyruvate sulfurtransferase: an enzyme at the crossroads of sulfane sulfur trafficking. Biol Chem. 2020; 402(3):223-237. DOI: 10.1515/hsz-2020-0249. View

Peleli M, Bibli S, Li Z, Chatzianastasiou A, Varela A, Katsouda A . Cardiovascular phenotype of mice lacking 3-mercaptopyruvate sulfurtransferase. Biochem Pharmacol. 2020; 176:113833. PMC: 7657663. DOI: 10.1016/j.bcp.2020.113833. View

Nagahara N, Yoshii T, Abe Y, Matsumura T . Thioredoxin-dependent enzymatic activation of mercaptopyruvate sulfurtransferase. An intersubunit disulfide bond serves as a redox switch for activation. J Biol Chem. 2006; 282(3):1561-9. DOI: 10.1074/jbc.M605931200. View

Huang X, Xiang L, Li Y, Zhao Y, Zhu H, Xiao Y . Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer. Cell Physiol Biochem. 2018; 47(2):590-603. DOI: 10.1159/000490015. View

Kimura Y, Toyofuku Y, Koike S, Shibuya N, Nagahara N, Lefer D . Identification of H2S3 and H2S produced by 3-mercaptopyruvate sulfurtransferase in the brain. Sci Rep. 2015; 5:14774. PMC: 4594004. DOI: 10.1038/srep14774. View

10.

Shibuya N, Kimura H . Production of hydrogen sulfide from d-cysteine and its therapeutic potential. Front Endocrinol (Lausanne). 2013; 4:87. PMC: 3712494. DOI: 10.3389/fendo.2013.00087. View

11.

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

12.

Wahafu W, Gai J, Song L, Ping H, Wang M, Yang F . Increased HS and its synthases in urothelial cell carcinoma of the bladder, and enhanced cisplatin-induced apoptosis following HS inhibition in EJ cells. Oncol Lett. 2018; 15(6):8484-8490. PMC: 6004664. DOI: 10.3892/ol.2018.8373. View

13.

Matyasova K, Soltysova A, Babula P, Krizanova O, Liskova V . Role of the 3-mercaptopyruvate sulfurtransferase in colon/colorectal cancers. Eur J Cell Biol. 2024; 103(2):151415. DOI: 10.1016/j.ejcb.2024.151415. View

14.

Wang J, Yang Y, Sun F, Luo Y, Yang Y, Li J . ALKBH5 attenuates mitochondrial fission and ameliorates liver fibrosis by reducing Drp1 methylation. Pharmacol Res. 2022; 187:106608. DOI: 10.1016/j.phrs.2022.106608. View

15.

Tao B, Wang R, Sun C, Zhu Y . 3-Mercaptopyruvate Sulfurtransferase, Not Cystathionine β-Synthase Nor Cystathionine γ-Lyase, Mediates Hypoxia-Induced Migration of Vascular Endothelial Cells. Front Pharmacol. 2017; 8:657. PMC: 5611563. DOI: 10.3389/fphar.2017.00657. View

16.

Thanki K, Nicholls M, Gajjar A, Senagore A, Qiu S, Szabo C . Consensus Molecular Subtypes of Colorectal Cancer and their Clinical Implications. Int Biol Biomed J. 2017; 3(3):105-111. PMC: 5557054. View

17.

Gavard J, Gutkind J . VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol. 2006; 8(11):1223-34. DOI: 10.1038/ncb1486. View

18.

Budczies J, von Winterfeld M, Klauschen F, Bockmayr M, Lennerz J, Denkert C . The landscape of metastatic progression patterns across major human cancers. Oncotarget. 2014; 6(1):570-83. PMC: 4381616. DOI: 10.18632/oncotarget.2677. View

19.

Toohey J, Cooper A . Thiosulfoxide (sulfane) sulfur: new chemistry and new regulatory roles in biology. Molecules. 2014; 19(8):12789-813. PMC: 4170951. DOI: 10.3390/molecules190812789. View

20.

Nagahara N, Ito T, Kitamura H, Nishino T . Tissue and subcellular distribution of mercaptopyruvate sulfurtransferase in the rat: confocal laser fluorescence and immunoelectron microscopic studies combined with biochemical analysis. Histochem Cell Biol. 1998; 110(3):243-50. DOI: 10.1007/s004180050286. View