ArticleCancer cell international2026
IL-12p40 drives oral squamous cell carcinoma progression via MMPs and IL-12Rβ1/STAT3 signaling.
Article in Cancer cell international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOral squamous cell carcinoma (OSCC) is an aggressive head and neck malignancy with frequent lymphatic metastasis and poor clinical outcomes. IL-12p40, a shared subunit of IL-12 and IL-23, can engage IL-12Rβ1, but its role in OSCC tumor-cell responses remains unclear. This study investigated whether IL-12p40 promotes OSCC progression and explored the underlying IL-12Rβ1/STAT3/MMP pathway.
methodsIL-12p40 expression was examined by immunohistochemistry in 90 OSCC tissues and 60 adjacent oral mucosa samples, and serum IL-12p40 was measured in 30 patients and 15 healthy controls. SCC9 and CAL33 cells were treated with recombinant IL-12p40, anti-IL-12p40 antibody, Stattic, or GM6001. Proliferation, wound healing, migration, invasion, and colony formation were assessed. RNA sequencing, quantitative real-time PCR, western blotting, IL-12Rβ1 silencing, and shRNA-mediated STAT3 knockdown were used for mechanistic validation. Subcutaneous xenograft, orthotopic tongue tumor, and lymphatic metastasis models were established. Statistical analyses included t tests, analysis of variance, chi-square or Fisher's exact tests, Kaplan-Meier analysis, Cox regression, and receiver operating characteristic analysis.
resultsIL-12p40 was elevated in OSCC tissues and patient serum. High tissue IL-12p40 expression was associated with lymph-node metastasis and poorer overall survival. IL-12p40 enhanced OSCC cell proliferation, migration, invasion, and colony formation in vitro and promoted tumor growth and lymphatic dissemination in vivo. Mechanistically, IL-12p40 activated IL-12Rβ1/STAT3 signaling and increased MMP2/MMP9 expression. IL-12Rβ1 silencing, STAT3 inhibition, STAT3 knockdown, and GM6001-mediated MMP blockade attenuated these effects.
conclusionsIL-12p40 promotes OSCC progression through an IL-12Rβ1/STAT3/MMP-related pathway, suggesting a candidate mechanism that warrants further therapeutic validation.
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