On the role of cystatin C in cancer progression
Abstract
Cystatin C (Cyst C) is an endogenous inhibitor of lysosomal cysteine proteinases, which has been shown to play a role in several normal and pathological processes. Interestingly, a growing number of experimental and clinical studies suggest that this inhibitor also appears to be implicated in the malignant progression of various human tumors. However, the role of Cyst C in malignant diseases is still controversial as these studies have highlighted that this protein may function either as tumor suppressor or tumor promoter. The specific mechanisms underlying these opposing effects at present remain murky and are the subject of many current investigations. On the other hand, a complete knowledge of these mechanisms is of clinical interest in order to develop new, effective antitumor treatments based on the appropriate use of natural and/or synthetic cysteine proteinase inhibitors. This paper discusses the current findings regarding the role of Cyst C in cancer progression and the clinical implications emerging from these studies.
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Cystatin C has tumor-suppressive properties mainly through its inhibitory action on cysteine cathepsins, thereby inhibiting tumor cell invasion and metastasis.
“it has also demonstrated tumor-suppressive properties, mainly through its inhibitory action on cysteine cathepsins, enzymes that regulate extracellular matrix (ECM) degradation and remodeling, thereby inhibiting tumor cells invasion and metastasis12.”
From Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors (2025) · cites this paper as [12]
Cites
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Cystatin C in aging and in Alzheimer’s disease
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Cystatin C Antagonizes Transforming Growth Factor β Signaling in Normal and Cancer Cells
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Macrophage responses to interferon-γ are dependent on cystatin C levels
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Zhang, C., He, Y., Liu, X., Xie, J., Fang, M., Yang, X., Huang, R., Lou, Q., Li, B., Gupta, A., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02462-x · Cited by 2 · see citing works
- Authors
- Leto, G., Crescimanno, M., & Flandina, C.
- Affiliations
- University of Palermo (IT)
- Corresponding author
- Leto, Gaetano
- ORCID
- Leto, Gaetano
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 202
- Pages
- 152-160
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2797406812
- Cited by
- 84
- References
- 4
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 25 · 2022: 13 · 2021: 5 · 2020: 9 · 2019: 6
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Funders
- Italian Ministry of University and Research (ORPA052247, ORPA07MN29)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- cystatin C, tumor progression, cysteine protease inhibitors, lysosomal cysteine proteases, tumor suppressor, tumor promoters, cancer therapy
- MeSH terms
- Animals, Humans, Neoplasm Metastasis, Neoplasms, Disease Progression, Cystatin C
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