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

J Cell Physiol. 2022 Dec;237(12):4551-4562. doi: 10.1002/jcp.30902. Epub 2022 Oct 19.

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.

Keywords: IL-1; MMP-13; gp130; metastasis; oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Cytokine Receptor gp130
  • Humans
  • Interleukin-11
  • Matrix Metalloproteinase 13 / genetics
  • Mouth Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Transcription Factor AP-1

Substances

  • Cytokine Receptor gp130
  • Interleukin-11
  • Matrix Metalloproteinase 13
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Transcription Factor AP-1
  • IL11 protein, human
  • MMP13 protein, human