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
p120(ctn) 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
delta-catenin/NPRAP/
neurojungin (CTNND2) and
p120(ctn) (CTNND1) provides a common motif for their interactions. Recently, crystallographic resolution of the JMD of
p120(ctn) further highlighted possibilities of intervening between interactions of
p120(ctn) subfamily
proteins and
E-cadherin for designing anti-
cancer therapeutics. For most epithelial
cancers, studies have demonstrated a reduction of
p120(ctn) expression or alteration of its subcellular distribution. On the other hand,
delta-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
p120(ctn) (CTNND1) gene amplification in
lung cancer. One mechanism by which
delta-catenin and
p120(ctn) may play a role in
carcinogenesis is their competitive binding to
E-cadherin through the JMD. The other presents the first vigorous characterization of
delta-catenin overexpression in
lung cancer. Unexpectedly, the authors observed that
delta-catenin promotes malignant phenotypes of
non-small cell lung cancer by non-competitive binding to
E-cadherin with
p120(ctn) in the cytoplasm. Looking towards the future, the understanding of
delta-catenin and
p120(ctn) with and beyond their localization at the cell-cell junction should provide further insight into their roles in
cancer pathogenesis.