Nuclear cysteine cathepsin variants in thyroid carcinoma cells

Tedelind, Sofia; Poliakova, Kseniia; Valeta, Amanda; Hunegnaw, Ruth; Yemanaberhan, Eyoel Lemma; Heldin, Nils-Erik; Kurebayashi, Junichi; Weber, Ekkehard; Kopitar-Jerala, Nata?a; Turk, Boris; Bogyo, Matthew; Brix, Klaudia (2010). Nuclear cysteine cathepsin variants in thyroid carcinoma cells. Biological chemistry, 391(8), pp. 923-35. Berlin: De Gruyter 10.1515/BC.2010.109

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The cysteine peptidase cathepsin B is important in thyroid physiology by being involved in thyroid prohormone processing initiated in the follicular lumen and completed in endo-lysosomal compartments. However, cathepsin B has also been localized to the extrafollicular space and is therefore suggested to promote invasiveness and metastasis in thyroid carcinomas through, e.g., ECM degradation. In this study, immunofluorescence and biochemical data from subcellular fractionation revealed that cathepsin B, in its single- and two-chain forms, is localized to endo-lysosomes in the papillary thyroid carcinoma cell line KTC-1 and in the anaplastic thyroid carcinoma cell lines HTh7 and HTh74. This distribution is not affected by thyroid stimulating hormone (TSH) incubation of HTh74, the only cell line that expresses a functional TSH-receptor. Immunofluorescence data disclosed an additional nuclear localization of cathepsin B immunoreactivity. This was supported by biochemical data showing a proteolytically active variant slightly smaller than the cathepsin B proform in nuclear fractions. We also demonstrate that immunoreactions specific for cathepsin V, but not cathepsin L, are localized to the nucleus in HTh74 in peri-nucleolar patterns. As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Poliakova, Kseniia

ISSN:

1431-6730

Publisher:

De Gruyter

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:12

Last Modified:

07 Nov 2014 07:51

Publisher DOI:

10.1515/BC.2010.109

PubMed ID:

20536394

Web of Science ID:

000281198700010

URI:

https://boris.unibe.ch/id/eprint/2270 (FactScience: 204661)

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