Cysteine protease I29 propeptide from Calotropis procera R. Br. As a potent cathepsin L inhibitor and its suppressive activity in breast cancer metastasis.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
05 Oct 2024
Historique:
received: 07 05 2024
accepted: 18 09 2024
medline: 6 10 2024
pubmed: 6 10 2024
entrez: 5 10 2024
Statut: epublish

Résumé

Breast cancer metastasis is associated with a poor prognosis and a high rate of mortality. Cathepsin L (CTSL) is a lysosomal cysteine protease that promotes tumor metastasis by degrading the extracellular matrix. Gene set enrichment analysis revealed that CTSL expression was higher in tumorous than in non-tumorous tissues of breast cancer patients and that high-level CTSL expression correlated positively with the epithelial-mesenchymal transition. Therefore, we hypothesized that inhibiting CTSL activity in tumor cells would prevent metastasis. In this study, we characterized the inhibitory activity of SnuCalCpI15, the I29 domain of a CTSL-like cysteine protease from Calotropis procera R. Br., and revealed that the propeptide stereoselectively inhibited CTSL in a reversible slow-binding manner, with an inhibitory constant (K

Identifiants

pubmed: 39368988
doi: 10.1038/s41598-024-73578-3
pii: 10.1038/s41598-024-73578-3
doi:

Substances chimiques

Cathepsin L EC 3.4.22.15
Cysteine Proteinase Inhibitors 0
CTSL protein, human EC 3.4.22.15

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

23218

Subventions

Organisme : Rural Development Administration, Republic of Korea
ID : RS-2021-RD009467
Organisme : National Research Foundation of Korea
ID : NRF-2022R1A2C1011914

Informations de copyright

© 2024. The Author(s).

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Auteurs

Yong-Jin Kwon (YJ)

Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
Department of Cosmetic Science, Kyungsung University, Busan, 48434, Republic of Korea.

Juno Lee (J)

Center for Agricultural Microorganism and Enzyme, Seoul National University, Seoul, 08826, Republic of Korea.
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

Eun-Bi Seo (EB)

Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

Juchan Lee (J)

Department of Agricultural Biotechnology, Seoul National University College of Agricultural and Life Sciences, Seoul, 08826, Republic of Korea.

Jaehyeon Park (J)

Department of Agricultural Biotechnology, Seoul National University College of Agricultural and Life Sciences, Seoul, 08826, Republic of Korea.

Seul-Ki Kim (SK)

Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

Hyunjong Yu (H)

Major of Food Science and Biotechnology, Division of Bio-Convergence, Kyonggi University, Suwon, 16227, Republic of Korea.

Sang-Kyu Ye (SK)

Department of Pharmacology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.
Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.
Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.
Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.
Wide River Institute of Immunology, Seoul National University, Hongcheon, 25159, Republic of Korea. sangkyu@snu.ac.kr.

Pahn-Shick Chang (PS)

Center for Agricultural Microorganism and Enzyme, Seoul National University, Seoul, 08826, Republic of Korea. pschang@snu.ac.kr.
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea. pschang@snu.ac.kr.
Department of Agricultural Biotechnology, Seoul National University College of Agricultural and Life Sciences, Seoul, 08826, Republic of Korea. pschang@snu.ac.kr.
Center for Food and Bioconvergence, Seoul National University, Seoul, 08826, Republic of Korea. pschang@snu.ac.kr.

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