Significance of nuclear cathepsin V in normal thyroid epithelial and carcinoma cells

Alaa Al-Hashimi, Vaishnavi Venugopalan, Naphannop Sereesongsaeng, Sofia Tedelind, Alexandra M. Pinzaru, Zeynep Hein, Sebastian Springer, Ekkehard Weber, Dagmar Führer, Christopher J. Scott, Roberta E. Burden, Klaudia Brix*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Altered expression and/or localization of cysteine cathepsins is believed to involve in thyroid diseases including cancer. Here, we examined the localization of cathepsins B and V in human thyroid tissue sections of different pathological conditions by immunolabeling and morphometry. Cathepsin B was mostly found within endo-lysosomes as expected. In contrast, cathepsin V was detected within nuclei, predominantly in cells of cold nodules, follicular and papillary thyroid carcinoma tissue, while it was less often detected in this unusual localization in hot nodules and goiter tissue. To understand the significance of nuclear cathepsin V in thyroid cells, this study aimed to establish a cellular model of stable nuclear cathepsin V expression. As representative of a specific form lacking the signal peptide and part of the propeptide, N-terminally truncated cathepsin V fused to eGFP recapitulated the nuclear localization of endogenous cathepsin V throughout the cell cycle in Nthy-ori 3-1 cells. Interestingly, the N-terminally truncated cathepsin V-eGFP was more abundant in the nuclei during S phase. These findings suggested a possible contribution of nuclear cathepsin V forms to cell cycle progression. Indeed, we found that N-terminally truncated cathepsin V-eGFP expressing cells were more proliferative than those expressing full-length cathepsin V-eGFP or wild type controls. We conclude that a specific molecular form of cathepsin V localizes to the nucleus of thyroid epithelial and carcinoma cells, where it might involve in deregulated pathways leading to hyperproliferation. These findings highlight the necessity to better understand cathepsin trafficking in health and disease. In particular, cell type specificity of mislocalization of cysteine cathepsins, which otherwise act in a functionally redundant manner, seems to be important to understand their non-canonical roles in cell cycle progression.

Original languageEnglish
Article number118846
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1867
Issue number12
Early online date07 Sep 2020
DOIs
Publication statusEarly online date - 07 Sep 2020

Keywords

  • Cysteine cathepsins
  • Non-canonical trafficking
  • Nuclear forms
  • Proliferation-promoting
  • Thyroid cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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