STAT1-TCTN3 axis drives papillary thyroid carcinoma progression by accelerating the cell cycle and promoting tumor cell migration and invasion.

Papillary thyroid carcinoma (PTC) lacks reliable molecular biomarkers and effective therapeutic targets. In this study, we investigated whether Signal Transducer and Activator of Transcription 1 (STAT1) promote PTC progression through regulation of tectonic family member 3 (TCTN3). Integrated analyses of TCGA and external datasets identified TCTN3 as a candidate oncogenic factor. Its expression was validated in paired PTC tissues and cell lines using RT-qPCR and western blotting. Functional assays, including CCK-8, EdU incorporation, colony formation, flow cytometric cell-cycle analysis, and Transwell migration/invasion assays, were performed following gain and loss of function of STAT1 and TCTN3. In vivo tumorigenicity was evaluated using nude mouse xenograft models and H&E. TCTN3 was consistently upregulated in PTC and enriched in cell-cycle related pathways. TCTN3 silencing suppressed proliferation, S-phase entry, migration, invasion, and tumor growth, whereas overexpression exerted opposite effects, accompanied by changes in PCNA, Cyclin D1, CDK4/6, MMP2, MMP9, and E-cadherin. STAT1 expression positively correlated with TCTN3 levels and modulated its expression. Chromatin immunoprecipitation and luciferase reporter assays demonstrated direct binding of STAT1 to the TCTN3 promoter, while co-immunoprecipitation confirmed the absence of direct protein interaction. STAT1 depletion phenocopied TCTN3 knockdown, and re-expression of TCTN3 rescued STAT1-deficient phenotypes. Our findings identify a STAT1-TCTN3 regulatory axis that drives cell-cycle progression, migration, and tumor growth in PTC, establishing this pathway as a mechanistically defined contributor to disease progression and a potential therapeutic target.