Downregulation of LGI1 promotes tumor metastasis in esophageal squamous cell carcinoma

Carcinogenesis. 2014 May;35(5):1154-61. doi: 10.1093/carcin/bgu040. Epub 2014 Feb 7.

Abstract

Here, we report the characterization of a candidate tumor suppressor gene leucine-rich glioma inactivated 1 (LGI1) in human esophageal squamous cell carcinoma (ESCC). Downregulation of LGI1 has been detected in approximately 50% of primary ESCCs, which was significantly associated with advanced clinical stage (P < 0.001), lymph node metastasis (P < 0.001), tumor invasion (P = 0.009) and poor disease-specific survival (P < 0.001). Functional studies found that LGI1 could inhibit cell growth, clonogenicity, cell motility and tumor formation in nude mice. Mechanistic investigations suggested that LGI1 acted through extracellular signal-regulated kinase (ERK1/2) signaling to downregulate matrix metalloproteinase (MMP)-3 expression and subsequently suppressed tumor metastasis. Taken together, our study revealed that LGI1 plays an important tumor suppressive role in the development and progression of ESCC, with possible application in clinics as a biomarker and a potential new therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Down-Regulation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Matrix Metalloproteinase 3 / metabolism
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Proteins / genetics*
  • RNA Interference
  • Tumor Suppressor Proteins / genetics

Substances

  • LGI1 protein, human
  • Proteins
  • Tumor Suppressor Proteins
  • Matrix Metalloproteinase 3