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

Lioni M, Brafford P, Andl C, Rustgi A, El-Deiry W, Herlyn M, Smalley KS
Am J Pathol. 2007 170 (2): 709-21

PMID: 17255337 · PMCID: PMC1851859 · 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.

MeSH Terms (15)

Cadherins Carcinoma, Squamous Cell Cell Differentiation Cell Line, Tumor Cell Transformation, Neoplastic Claudins Esophageal Neoplasms Esophagus Gene Expression Regulation, Neoplastic Humans Keratinocytes Membrane Proteins Neoplasm Invasiveness Neoplasm Proteins RNA, Small Interfering

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