{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:58:15Z","timestamp":1790197095418,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cSirius\u201d Federal Territory \u201cScientific and technological development of the \u201cSirius\u201d Federal Territory\u201d","award":["22-03"],"award-info":[{"award-number":["22-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cathepsin B (CTSB), a lysosomal cysteine protease, plays pivotal roles in cellular homeostasis and pathology, including cancer progression. This study investigates the regulatory interplay between CTSB and Stefin A (STFA), an endogenous inhibitor of cysteine proteases, in renal and prostate cancer cells. Using plasmid-based overexpression and silencing systems, we demonstrated that overexpressing STFA significantly reduces CTSB activity and protein levels, while silencing STFA leads to elevated CTSB activity and expression in cancer cells but not in non-cancerous cells (embryonic kidney cells\u2014Hek293T and endothelial cells\u2014EA.hy926). Furthermore, STFA modulates the subcellular distribution of CTSB, with STFA overexpression reducing nuclear CTSB levels and silencing inducing cytoplasmic accumulation in cancer cells. Colocalization analysis confirms a direct interaction between STFA and CTSB, highlighting the spatial coordination necessary for effective protease inhibition. These findings underscore the critical role of the CTSB-STFA axis in maintaining proteolytic balance and suggest potential therapeutic strategies targeting this interaction in renal carcinoma and other cancers.<\/jats:p>","DOI":"10.3390\/ijms26199321","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T12:15:31Z","timestamp":1758716131000},"page":"9321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stefin A Regulation of Cathepsin B Expression and Localization in Cancerous and Non-Cancerous Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5035-8445","authenticated-orcid":false,"given":"Anastasiia O.","family":"Syrocheva","sequence":"first","affiliation":[{"name":"Research Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6730-1858","authenticated-orcid":false,"given":"Ekaterina P.","family":"Kolesova","sequence":"additional","affiliation":[{"name":"Research Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0985-6545","authenticated-orcid":false,"given":"Alessandro","family":"Parodi","sequence":"additional","affiliation":[{"name":"Research Center for Translational Medicine, Sirius University of Science and Technology, 354340 Sochi, Russia"},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3046-4565","authenticated-orcid":false,"suffix":"Jr.","given":"Andrey A.","family":"Zamyatnin","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"},{"name":"Department of Biological Chemistry, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cai, Z., Xu, S., and Liu, C. 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