Changes in active cysteine cathepsinsin lysosomes from tissues thyroid papillary carcinomas with various biologicalcharacteristics

Ov, Kalinichenko; Tm, Myshunina; Tron'ko,

doi:10.15407/fz59.05.011

Cited by 1 publication

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References 29 publications

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“…Cysteine cathepsins also play a role in thyroid cancer, a notion derived from studying cathepsin B in particular [6][7][8]. Cathepsin B expression is upregulated and it is secreted toward the extracellular space of thyroid carcinoma cells in situ, suggesting an initial contribution of cathepsin B to tumor cell invasiveness and metastasis through excessive degradation of the extracellular matrix [6,7,[9][10][11]. However, specific forms of cathepsin B were detected in thyroid carcinoma cell nuclei, where they might be involved in histone processing [8].…”

Section: Introductionmentioning

confidence: 99%

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

Al-Hashimi

Venugopalan

Sereesongsaeng

et al. 2020

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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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 nodule 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 Nterminally 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.

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