Interleukin-11/gp130 upregulates MMP-13 expression and cell migration in OSCC by activating PI3K/Akt and AP-1 signaling.

ABSTRACT

Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.