Expression of
E-cadherin has a central role in maintaining epithelial morphology. In solid
tumors, reduction of
E-cadherin results in disruption of intercellular contacts. Consequently, cells lose adhesive properties and gain more invasive mesenchymal properties. Nevertheless, the mechanism of
E-cadherin regulation is not completely elucidated. Here we analyzed the distribution of
E-cadherin expression at the cell level in human
hepatocellular carcinoma, in which human liver
paraffin blocks from 25
hepatocellular carcinoma patients were prepared from cancerous (CA) and noncancerous areas (NCA). In situ hybridization (ISH) was performed to detect
E-cadherin and
hypoxia-induced factor-1α (HIF1α) mRNAs and immunohistochemistry to
stain E-cadherin protein. In parallel,
RNA was extracted from CA and NCA, and
E-cadherin and HIF1α were quantified by quantitative reverse transcription PCR. ISH revealed abundant
E-cadherin mRNA in nuclei of
hepatocellular carcinoma cells (HCCs), whereas immunohistochemistry showed depletion of
E-cadherin protein from these areas. In sections of NCA,
E-cadherin mRNA was also found in the cytosol, and
E-cadherin protein was detected on the membrane of cells. Experiments in cell lines confirmed
E-cadherin mRNA in nuclei of cells negative for
E-cadherin protein. HIF1α expression is elevated in CAs, which is associated with a clear cytosolic staining for this
mRNA. Our results demonstrate that E-caderhin
mRNA is selectively retained in nuclei of HCCs, whereas other mRNAs are still exported, suggesting that translocation of
E-cadherin mRNA from nuclei to cytoplasm has a role in regulating
E-cadherin protein levels during epithelial mesenchymal transition.