Dysregulation of claudin-7 leads to loss of E-cadherin expression and the increased invasion of esophageal squamous cell carcinoma cells

Am J Pathol. 2007 Feb;170(2):709-21. doi: 10.2353/ajpath.2007.060343.


The claudins constitute a 24-member family of proteins that are critical for the function and formation of tight junctions. Here, we examine the expression of claudin-7 in squamous cell carcinoma (SCC) of the esophagus and its possible role in tumor progression. In the normal esophagus, expression of claudin-7 was confined to the cell membrane of differentiated keratinocytes. However, in the tumor samples, claudin-7 expression is often lost or localized to the cytoplasm. Assaying esophageal SCC lines revealed variable expression of claudin-7, with some lacking expression completely. Knockdown of claudin-7 in SCC cell lines using a small interfering RNA approach led to decreased E-cadherin expression, increased cell growth, and enhanced invasion into a three-dimensional matrix. The opposite was observed when claudin-7 was overexpressed in esophageal SCC cells lacking both claudin-7 and E-cadherin. In this context, the claudin-7-overexpressing cells became more adhesive and less invasive associated with increased E-cadherin expression. In summary, we demonstrate that claudin-7 is mislocalized during the malignant transformation of esophageal keratinocytes. We also demonstrate a critical role for claudin-7 expression in the regulation of E-cadherin in these cells, suggesting this may be one mechanism for the loss of epithelial architecture and invasion observed in esophageal SCC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / biosynthesis*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Claudins
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophagus / metabolism
  • Esophagus / pathology
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / biosynthesis*
  • Neoplasm Invasiveness
  • Neoplasm Proteins
  • RNA, Small Interfering / biosynthesis*
  • RNA, Small Interfering / pharmacology


  • CLDN7 protein, human
  • Cadherins
  • Claudins
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering