Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs
Open accessAbstract
The main group of enzymes responsible for the collagen and other protein degradation in extracellular matrix (ECM) are matrix metalloproteinases (MMPs). Collagen is the main structural component of connective tissue and its degradation is a very important process in the development, morphogenesis, tissue remodeling, and repair. Typical structure of MMPs consists of several distinct domains. MMP family can be divided into six groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs. MMPs and their inhibitors have multiple biological functions in all stages of cancer development: from initiation to outgrowth of clinically relevant metastases and likewise in apoptosis and angiogenesis. MMPs and their inhibitors are extensively examined as potential anticancer drugs. MMP inhibitors can be divided into two main groups: synthetic and natural inhibitors. Selected synthetic inhibitors are in clinical trials on humans, e.g. synthetic peptides, non-peptidic molecules, chemically modified tetracyclines, and bisphosphonates. Natural MMP inhibitors are mainly isoflavonoids and shark cartilage.
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ECM may act as a barrier for drug delivery through increased tissue stiffness and desmoplasia, or as a gate for breaching the basement membrane to promote metastasis.
“ECM may act as a barrier for drug delivery through increased tissue stiffness and desmoplasia or a gate for breaching the basement membrane to promote metastasis [2, 122].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [122]
The sections on MMPs and cancer and on invasion and metastasis describe ECM barriers being broken down and ECM degradation facilitating cancer-cell migration and metastasis (page unavailable). The paper does not say that stiffness or desmoplasia makes the ECM a barrier to drug delivery. Its explicit discussion of basement-membrane disruption is about angiogenesis, not metastatic breaching. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSVMPs enzymatically degrade structural components of ECM and basement membranes, resulting in detachment of cells from basement membrane support, leading to apoptosis by anoikis.
“Snake venom metalloproteases (SVMPs) enzymatically degrade the structural components of the extracellular matrix and basement membranes, and this results in the detachment of cells from the basement membrane support, leading to apoptosis by a specialized mechanism called anoikis (Figure 2) [49,50,51].”
From Role of Regulated Cell Death Pathways in Snakebite Envenomation: Mechanisms, Crosstalk, and Therapeutic Opportunities (2026) · cites this paper as [51]
The sections “MMPs influence on angiogenesis” and “MMPs influence on apoptosis” describe basement-membrane and ECM degradation by MMPs and say MMPs may contribute to anoikis. “MMPs role in invasion and metastasis” links anoikis to loss of cell connection to the ECM. The paper does not establish the claimed sequence specifically for snake venom metalloproteases (SVMPs), and it hedges the MMP–anoikis link. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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Percentages, sums and reported differences re-computed from the paper’s own numbers.
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BackgroundAlangode, A., Rajasekhar, A., Sabu, J. J., Krishna, S., Anuja, D., Sreeja, A., Remesh, G., Kaladevi, A., & Nair, B. G. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156830
“Snake venom metalloproteases (SVMPs) enzymatically degrade the structural components of the extracellular matrix and basement membranes, and this results in the detachment of cells from the basement membrane support, leading to apoptosis by a specialized mechanism called anoikis (Figure 2) [49–51].”
- Authors
- Jabłońska-Trypuć, A., Matejczyk, M., & Rosochacki, S.
- Affiliations
- Department of Sanitary Biology and Biotechnology, Faculty of Civil Engineering and Environmental Engineering, Bialystok University of Technology, Białystok, Poland
- Bialystok University of Technology (PL)
- ORCID
- Matejczyk, Marzena
- Venue
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Publisher
- Informa UK Limited
- Published
- 2016-03-30
- Volume
- 31
- Issue
- sup1
- Pages
- 177-183
- ISSN
- 1475-6366 (ISSN-L)
- 1475-6374
- OpenAlex
- W2322375144
- Cited by
- 1,042
- References
- 48
- Citations by year
- 2026: 57 · 2025: 118 · 2024: 125 · 2023: 107 · 2022: 136 · 2021: 149 · 2020: 156 · 2019: 104 · 2018: 57 · 2017: 29 · 2016: 2 · 2015: 1
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Enzyme Inhibition and Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- matrix metalloproteinases, collagen degradation, extracellular matrix, matrix metalloproteinase inhibitors, anticancer agents, collagenase, gelatinase, stromelysin, matrilysin, membrane-type MMPs, metastasis, angiogenesis, apoptosis, tissue remodeling, synthetic inhibitors, natural inhibitors, isoflavonoids, shark cartilage, bisphosphonates, tetracycline
- MeSH terms
- Animals, Antineoplastic Agents, Collagen, Dose-Response Relationship, Drug, Extracellular Matrix, Humans, Neoplasms, Structure-Activity Relationship, Apoptosis, Matrix Metalloproteinases, Matrix Metalloproteinase Inhibitors
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