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

Tripti Tamhane, Robin W. Njenga, Roberta E. Burden, Heiko Büth, Gunhild M. Maelandsmo, Mads H. Haugen, Christopher J. Scott, Klaudia Brix*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.
Original languageEnglish
Pages (from-to)e11936
Number of pages17
JournalApplied Sciences
Volume11
Issue number24
Early online date15 Dec 2021
DOIs
Publication statusEarly online date - 15 Dec 2021

Keywords

  • aggresomes
  • cathepsin B
  • colorectal cancer
  • enhanced green fluorescent protein tagging
  • nuclear specific protease forms
  • protein engineering
  • protein misfolding
  • protein trafficking

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