MMP-11 promoted the oral cancer migration and Fak/Src activation

Oncotarget. 2017 May 16;8(20):32783-32793. doi: 10.18632/oncotarget.15824.

Abstract

Matrix metalloproteinase-11 (MMP-11) has been observed in most invasive human carcinomas. The current study investigated the association between the clinicopathological characteristics and MMP-11 expression in oral squamous cell carcinoma (OSCC) patients. Immunohistochemistry (IHC) staining was performed to assess MMP-11 expression in 279 patients with OSCC. In addition, the metastatic effects of the MMP-11 overexpression on the OSCC cells were also investigated. We found that MMP-11 expression was present in 118/279 (42.3%) cases and expression of MMP-11 was associated with higher incidence of lymph node metastasis and worse grade of tumor differentiation. Importantly, OSCC patients with strong expression of MMP-11 had a significantly lower survival rate (p=0.010). Furthermore, MMP-11 overexpression in OSCC cells increased in vitro cell migration. Mechanistically, MMP-11 increased the cell motility of OSCC cells through focal adhesion kinase/Src kinase (FAK/Src) pathway. In conclusion, our results revealed that the MMP-11 expression in OSCC samples can predict the progression, especially lymph node metastasis, and the survival of OSCC patients in Taiwan.

Keywords: FAK/Src pathway; matrix metalloproteinase; metastasis; oral squamous cell carcinoma; survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Disease Progression
  • Female
  • Focal Adhesion Kinase 1 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 11 / metabolism*
  • Middle Aged
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Grading
  • Neoplasm Staging
  • Signal Transduction
  • Survival Analysis
  • Up-Regulation
  • src-Family Kinases / metabolism*

Substances

  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • src-Family Kinases
  • MMP11 protein, human
  • Matrix Metalloproteinase 11