ArticleThe Biochemical journal2021
Simultaneous targeting of CD44 and MMP9 catalytic and hemopexin domains as a therapeutic strategy.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- A protein-small molecule conjugate as a bispecific inhibitor of proteases implicated in cancer metastasis.Scientific reports · 2026Article
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- A guide to the types, structures, and multifaceted functions of matrix metalloproteinases in cancer.The FEBS journal · 2026Review
- Integrating Single-Cell Profiling with Generative AI forMolecules (Basel, Switzerland) · 2026Article
- Sliding into Place: The Lymphatic Vessel Endothelial Hyaluronan Receptor LYVE-1 and Its Role as a Mediator of Cell Entry and Trafficking in the Lymphatics.Biomolecules · 2026Review
- Increased CD44 Expression in Endothelial Cells Induced by Advanced Glycation End Products Leads to Insufficient Maturation of Angiogenesis.Journal of cellular and molecular medicine · 2026Article
- Identification of potential molecular targets of luteolin in the treatment of hepatocellular carcinoma based on network pharmacology and transcriptome sequencing technology.Discover oncology · 2025Article
- Article
- Prognostic prediction using a gene signature developed based on exhausted T cells for liver cancer patients.Heliyon · 2024Article
- The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer.Theranostics · 2024Article
- SpaRx: elucidate single-cell spatial heterogeneity of drug responses for personalized treatment.Briefings in bioinformatics · 2023Article
- SpaRx: Elucidate single-cell spatial heterogeneity of drug responses for personalized treatment.bioRxiv : the preprint server for biology · 2023Article
- A New Model of Esophageal Cancers by Using a Detergent-Free Decellularized Matrix in a Perfusion Bioreactor.Bioengineering (Basel, Switzerland) · 2023Article
- Structure and computation-guided yeast surface display for the evolution of TIMP-based matrix metalloproteinase inhibitors.Frontiers in molecular biosciences · 2023Review
- A phase 1b study of andecaliximab in combination with S-1 plus platinum in Japanese patients with gastric adenocarcinoma.Scientific reports · 2022Article
- MMP9: A Tough Target for Targeted Therapy for Cancer.Cancers · 2022Review
- The interplay of EMT and stemness driving malignant transformation of Oral Submucous Fibrosis.Journal of oral biology and craniofacial researchArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crosstalk of the oncogenic matrix metalloproteinase-9 (MMP9) and one of its ligands, CD44, involves cleavage of CD44 by the MMP9 catalytic domain, with the CD44-MMP9 interaction on the cell surface taking place through the MMP9 hemopexin domain (PEX). This interaction promotes cancer cell migration and invasiveness. In concert, MMP9-processed CD44 induces the expression of MMP9, which degrades ECM components and facilitates growth factor release and activation, cancer cell invasiveness, and metastasis. Since both MMP9 and CD44 contribute to cancer progression, we have developed a new strategy to fully block this neoplastic process by engineering a multi-specific inhibitor that simultaneously targets CD44 and both the catalytic and PEX domains of MMP9. Using a yeast surface display technology, we first obtained a high-affinity inhibitor for the MMP9 catalytic domain, which we termed C9, by modifying a natural non-specific MMP inhibitor, N-TIMP2. We then conjugated C9 via a flexible linker to PEX, thereby creating a multi-specific inhibitor (C9-PEX) that simultaneously targets the MMP9 catalytic and PEX domains and CD44. It is likely that, via its co-localization with CD44, C9-PEX may compete with MMP9 localization on the cell surface, thereby inhibiting MMP9 catalytic activity, reducing MMP9 cellular levels, interfering with MMP9 homodimerization, and reducing the activation of downstream MAPK/ERK pathway signaling. The developed platform could be extended to other oncogenic MMPs as well as to other important target proteins, thereby offering great promise for creating novel multi-specific therapeutics for cancer and other diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.