{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:53:20Z","timestamp":1780354400383,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,16]],"date-time":"2019-03-16T00:00:00Z","timestamp":1552694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Triple-negative breast cancers (TNBCs) are more aggressive than other breast cancer (BC) subtypes and lack effective therapeutic options. Unraveling marker events of TNBCs may provide new directions for development of strategies for targeted TNBC therapy. Herein, we reported that Annexin A1 (AnxA1) and Cathepsin D (CatD) are highly expressed in MDA-MB-231 (TNBC lineage), compared to MCF-10A and MCF-7. Since the proposed concept was that CatD has protumorigenic activity associated with its ability to cleave AnxA1 (generating a 35.5 KDa fragment), we investigated this mechanism more deeply using the inhibitor of CatD, Pepstatin A (PepA). Fourier Transform Infrared (FTIR) spectroscopy demonstrated that PepA inhibits CatD activity by occupying its active site; the OH bond from PepA interacts with a CO bond from carboxylic acids of CatD catalytic aspartate dyad, favoring the deprotonation of Asp33 and consequently inhibiting CatD. Treatment of MDA-MB-231 cells with PepA induced apoptosis and autophagy processes while reducing the proliferation, invasion, and migration. Finally, in silico molecular docking demonstrated that the catalytic inhibition comprises Asp231 protonated and Asp33 deprotonated, proving all functional results obtained. Our findings elucidated critical CatD activity in TNBC cell trough AnxA1 cleavage, indicating the inhibition of CatD as a possible strategy for TNBC treatment.<\/jats:p>","DOI":"10.3390\/ijms20061337","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T12:18:53Z","timestamp":1552911533000},"page":"1337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Inhibition of Triple-Negative Breast Cancer Cell Aggressiveness by Cathepsin D Blockage: Role of Annexin A1"],"prefix":"10.3390","volume":"20","author":[{"given":"Mariana Alves Pereira","family":"Z\u00f3ia","sequence":"first","affiliation":[{"name":"Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Van Petten","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Vecchi","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Teixeira Soares","family":"Mota","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG 38700-128, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius de Rezende","family":"Rodovalho","sequence":"additional","affiliation":[{"name":"Laboratory of Biosensors, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonielle Oliveira","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG 38700-128, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Ian Veloso","family":"Correia","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anielle Christine Almeida","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Isolation and Semiconductor Materials, Physics Institute, Federal University of Uberlandia, Uberlandia-MG 38408-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veridiana de Melo Rodrigues","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaise Gon\u00e7alves de","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"},{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas-MG 38700-128, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1803-4861","authenticated-orcid":false,"given":"Luiz Ricardo","family":"Goulart","sequence":"additional","affiliation":[{"name":"Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia-MG 38400-902, Brazil"},{"name":"Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Lancet Oncology (2018). 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