# QSOX1: A Mysterious Golgi-Localized Disulfide Bond Catalyst and an Emerging Cancer Regulator

## TL;DR

This paper reviews how QSOX1, a disulfide bond enzyme, contributes to cancer progression and its potential as a biomarker or therapeutic target.

## Contribution

The paper provides a comprehensive review of QSOX1's dual roles in cancer and highlights gaps in understanding its regulatory mechanisms.

## Key findings

- QSOX1 is upregulated in many cancers through multiple regulatory mechanisms.
- QSOX1 promotes tumor progression by enhancing matrix metalloproteinase activity and regulating the extracellular matrix.
- QSOX1 has both tumor-promoting and tumor-suppressive roles depending on the cancer context.

## Abstract

In this Commentary, we summarize recent advances in understanding the role of the Golgi-localized disulfide bond catalyst QSOX1 in human cancers. Disulfide bond formation is critical for proper protein folding and stability, and its dysregulation contributes to cancer progression by modulating extracellular matrix (ECM) organization and cell signaling. QSOX1 is a unique oxidoreductase that catalyzes de novo disulfide bond formation primarily in the Golgi apparatus and extracellular space, distinguishing it from classical ER-resident enzymes. QSOX1 is upregulated in many cancers through a combination of genetic, transcriptional, microenvironmental, and post-transcriptional mechanisms. Functionally, QSOX1 can promote tumor progression by enhancing matrix metalloproteinase activity, supporting cancer cell survival under oxidative stress, regulating ECM assembly, and fostering immune-suppressive tumor microenvironments. However, QSOX1 also exhibits tumor-suppressive functions in certain cancer contexts, underscoring its context-dependent roles. Although QSOX1 is emerging as a potential biomarker and therapeutic target, further studies are needed to define its regulatory mechanisms, substrates, and isoform-specific functions to enable effective clinical translation.

Quiescin sulfhydryl oxidase 1 (QSOX1) is a disulfide bond-forming enzyme with both disulfide isomerase and oxidoreductase activities. It plays an important role in protein folding, stability, and secretion. Growing evidence demonstrates that QSOX1 is upregulated in multiple cancer types and influences key behaviors of cancer cells, including proliferation, migration, invasion, and metastasis. Elevated QSOX1 expression is also associated with tumor malignancy and disease relapse. However, the molecular mechanisms by which QSOX1 drives cancer progression remain incompletely understood. In this review, we summarize current knowledge of QSOX1 expression and regulation in cancer, discuss its functional roles, and highlight key unanswered questions to warrant further investigation.