Quiescin sulfhydryl oxidase 1 (QSOX1) (QSOX1)

Quiescin sulfhydryl oxidase 1 (QSOX1) is a flavin-linked enzyme that catalyzes the de novo formation of disulfide bonds in proteins, primarily within the Golgi apparatus and the extracellular space [UniProt, MDPI]. Unlike the classical protein disulfide isomerases found in the endoplasmic reticulum, QSOX1 directly reduces molecular oxygen to hydrogen peroxide while oxidizing thiol groups in substrate proteins to disulfides [NCBI, UniProt]. This activity is essential for the proper folding and stability of various secreted and membrane-bound proteins, particularly those involved in the assembly of the extracellular matrix (ECM), such as laminin [Wikipedia, UniProt]. In many aggressive human cancers, including pancreatic, breast, and lung carcinomas, QSOX1 is significantly overexpressed and promotes tumor cell migration, invasion, and metastasis by modulating ECM architecture and activating matrix metalloproteinases [MDPI, PMC, PubMed: 31575656]. Consequently, QSOX1 has emerged as a promising therapeutic target and a potential diagnostic biomarker for early cancer detection [Patsnap, ClinicalTrials.gov]. Experimental inhibitors, such as the small molecule SBI-183 and the monoclonal antibody MAb492.1, have demonstrated the ability to suppress tumor growth and metastasis in preclinical models by disrupting the enzyme's catalytic function [PubMed: 31575656, Innoget]. Additionally, QSOX1 expression has been linked to drug resistance and sensitivity, such as promoting sorafenib-induced ferroptosis in hepatocellular carcinoma [PMC: 10.1038/s41419-021-03812-w].

Other names

Sulfhydryl oxidase 1hQSOXQuiescin Q6Q6QSCN6Thiol oxidase 1

Inhibition of enzymatic sulfhydryl oxidase activity through catalytic site binding or steric hindrance, leading to impaired disulfide bond formation and disrupted extracellular matrix assembly [PubMed: 31575656, Innoget, Patsnap].