Matrix metalloproteinase-14 (MMP-14) downregulation inhibits esophageal squamous cell carcinoma cell migration, invasion, and proliferation

Thorac Cancer. 2020 Nov;11(11):3168-3174. doi: 10.1111/1759-7714.13636. Epub 2020 Sep 15.

Abstract

Background: Matrix metalloproteinase-14 (MMP-14) is known to be a key regulator of oncogenesis and tumor progression. The present study was designed to assess the relationship between the downregulation of MMP-14 and the in vitro proliferative, migratory, and invasive activity of esophageal squamous cell carcinoma (ESCC) cells.

Methods: MMP-14 expression in human ESCC and paracancerous normal esophageal tissue samples was evaluated via immunohistochemistry, and correlations between MMP-14 staining and patient clinicopathological features were examined. In addition, siRNA was used to knockdown MMP-14 in ESCC cells, and the proliferation and invasive activity of these cells were then evaluated via MTT and Transwell assays, respectively. Flow cytometry was additionally used to assess cell cycle progression, while Western blotting was employed to measure protein levels within these cells.

Results: ESCC samples were found to exhibit MMP-14 overexpression relative to paracancerous tissue samples, and this overexpression was positively correlated with tumor T classification (T1-2 vs. T3; P < 0.05), N classification (negative vs. positive; P < 0.001), degree of differentiation (G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05) and clinical stage (I-IIA vs. IIB-III; P < 0.05). When MMP-14 was knocked down in ESCC cells, this induced cell cycle arrest, impairing their proliferative and invasive activity.

Conclusions: MMP-14 is a key regulator of the proliferation and invasion of ESCC cells, making it a viable therapeutic target for the treatment of this cancer.

Keywords: Esophageal squamous cell carcinoma; matrix metalloproteinase-14; tumor invasion.

MeSH terms

  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Disease Progression
  • Down-Regulation
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / enzymology*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / pathology
  • Humans
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness

Substances

  • MMP14 protein, human
  • Matrix Metalloproteinase 14