QSOX1 as a mediator of tumor–fibroblast crosstalk and a modulator of pulmonary tumor burden in lung adenocarcinoma

Quiescin sulfhydryl oxidase 1 (QSOX1), an enzyme that catalyzes disulfide bond formation, is expressed in various cancers, but its role in the tumor microenvironment (TME) remains unclear. Here, we investigated the role of QSOX1 in tumor–stromal interactions in lung adenocarcinoma (LUAD). Analysis of public datasets revealed elevated QSOX1 expression in early-stage LUAD and its association with poor prognosis. Given the central role of cancer-associated fibroblasts (CAFs) in extracellular matrix (ECM) organization and tumor progression, we examined whether QSOX1 expression in LUAD cells affects fibroblast activation. Modulation of QSOX1 expression in lung cancer cells altered CAF-associated marker expression, ECM deposition, collagen gel contraction, and fibroblast migration, accompanied by changes in YAP/TAZ and integrin β1/αV expression. QSOX1 was also expressed in stromal cells in normal lung tissue and was predominantly detected in fibroblasts. We therefore examined whether fibroblast QSOX1 affects tumor cell behavior and found that fibroblast QSOX1 influenced tumor cell migration and invasion in vitro. In vivo, QSOX1 deficiency was associated with reduced pulmonary tumor burden. Collectively, our findings suggest that QSOX1 acts as a mediator of lung cancer–fibroblast crosstalk and a modulator of pulmonary tumor burden in early-stage LUAD.