Trafficking of Full-Length and N-Terminally Truncated Cathepsin B in Human Colorectal Carcinoma Cells

Featured Application Full-length cathepsin B is sorted to endo-lysosomes of colorectal carcinoma cells, while N-terminally truncated cathepsin B accumulates in aggresomes. Cathepsin B is an endo-lysosomal cysteine protease. However, its increased expression and altered localization to the extracellular space, to mitochondria, or to the nucleus has been linked to tumor progression. In the present study, we show enhanced levels of cathepsin B in adenocarcinoma tissue in comparison to adjacent normal colon. Additionally, cathepsin B was observed in the nuclear compartment of mucosal cells in adenocarcinoma tissue samples and in the nuclei of the colorectal carcinoma cell line HCT116. Accordingly, a distinct 40-kDa form of cathepsin B was detected in HCT116 cells, which is proposed to represent a specific form lacking the signal peptide and parts of the propeptide. Trafficking studies with an EGFP-tagged N-terminally truncated form, mimicking the 40-kDa form, demonstrated accumulation in aggresome-like inclusion bodies, while EGFP-tagged full-length cathepsin B revealed regular sorting to endo-lysosomes. We conclude that the identity of nuclear cathepsin B in colorectal adenocarcinoma (in situ) and in carcinoma cells (in vitro) cannot be attributed to either full-length or 40-kDa N-terminally truncated cathepsin B forms. Hence, future studies are needed to demonstrate which form/s of cathepsin B may be sorted to the nuclei of colorectal carcinoma cells, and whether redundant regulation of related cathepsin expression occurs.

Automated summary

The study reveals increased levels of cathepsin B in adenocarcinoma tissue compared to normal colon, and its localization in the nucleus of mucosal cells and colorectal carcinoma cells. A distinct 40kDa form of cathepsin B was detected in HCT116 cells, suggesting a specific form lacking a signal peptide and part of the propeptide. Further research is needed to determine which form/s of cathepsin B may be sorted to the nuclei of colorectal carcinoma cells and if redundant regulation of related cathepsin expression occurs.