Stable E‐cadherin‐based adherens junctions are pivotal in maintaining epithelial tissue integrity and are the major barrier for epithelial cancer metastasis. Proteins of the p120ctn subfamily have emerged recently as critical players for supporting this stability. The identification of the unique juxtamembrane domain (JMD) in E‐cadherin that binds directly to δ‐catenin/NPRAP/neurojungin ( CTNND2 ) and p120ctn ( CTNND1 ) provides a common motif for their interactions. Recently, crystallographic resolution of the JMD of p120ctn further highlighted possibilities of intervening between interactions of p120ctn subfamily proteins and E‐cadherin for designing anti‐cancer therapeutics. For most epithelial cancers, studies have demonstrated a reduction of p120ctn expression or alteration of its subcellular distribution. On the other hand, δ‐catenin, a primarily neural‐enriched protein in the brain of healthy individuals, is up‐regulated in all cancer types that have been studied to date. Two research articles in the September 2010 issue of The Journal of Pathology increase our understanding of the involvement of these proteins in lung cancer. One reports the identification of rare p 120 ctn ( CTNND1 ) gene amplification in lung cancer. One mechanism by which δ‐catenin and p120ctn may play a role in carcinogenesis is their competitive binding to E‐cadherin through the JMD. The other presents the first vigorous characterization of δ‐catenin overexpression in lung cancer. Unexpectedly, the authors observed that δ‐catenin promotes malignant phenotypes of non‐small cell lung cancer by non‐competitive binding to E‐cadherin with p120ctn in the cytoplasm. Looking towards the future, the understanding of δ‐catenin and p120ctn with and beyond their localization at the cell–cell junction should provide further insight into their roles in cancer pathogenesis. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Invited Commentary for Castillo et al. Gene amplification of the transcription factor DP1 and CTNND1 in human lung cancer, Journal of Pathology, 2010; 222: 89–98. And for Zhang et al. δ‐Catenin promotes malignant phenotype of non‐small cell lung cancer by non‐competative binding to E‐cadherin with p120ctn in cytoplasm. Journal of Pathology, 2010; 222: 76–88.