QSOX2-Mediated Disulfide Bond Modification Enhances Tumor Stemness and Chemoresistance by Activating TSC2/mTOR/c-Myc Feedback Loop in Esophageal Squamous Cell Carcinoma.

ABSTRACT: Disulfide bond modification is critical in maintaining protein structure and activity, but its roles in regulating tumor stemness and chemoresistance remain underexplored. Here, Quiescin Sulfhydryl Oxidase 2 (QSOX2) is identified, a protein involved in disulfide bond formation, is highly expressed in esophageal squamous cell carcinoma (ESCC), and is associated with poor patient prognosis. Functional analyses demonstrated that QSOX2 overexpression markedly potentiated tumor stemness and further promoted chemoresistance, proliferation, and metastasis of ESCC cells. Mechanistically, QSOX2 enhances disulfide bond formation in TSC Complex Subunit 2 (TSC2), stabilizing TSC2-Akt interactions, facilitating phosphorylation of TSC2 at the Ser939 by Akt, and further activating mTOR/4E-BP1/c-Myc signa

SUBMITTER: Chen WM 

PROVIDER: S-EPMC12376698 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature