ArticleThe Journal of clinical investigation2017
Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
53 citing papers in PubMed, 77 citations in OpenAlex.
- Dynamic modulation of intercellular adhesion mediated by matriptase-EPCAM/Trop-2 axes is critical for cell extrusion, division, and collective migration.Cell adhesion & migration · 2026Article
- Trop-1/EpCAM Thr115 is a driver of hyperproliferative cell repair and of severe lung damage in COVID-19.iScience · 2026Article
- Matriptase proteolysis selectively drives disassembly and internalization of the claudin-7 complex while preserving E-cadherin.Human cell · 2026Article
- CLDN7: Epithelial gatekeeper from physiology to pathology‑roles in cancer and epithelial‑related diseases (Review).International journal of molecular medicine · 2026Review
- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- Bacterial Extracellular Vesicles in Aging: Mechanisms and Therapeutic Prospects.International journal of nanomedicine · 2026Review
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- Article
- Regulation of the Function and Expression of EpCAM.Biomedicines · 2024Review
- SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.Human molecular genetics · 2024Article
- Early-onset tufting enteropathy in HAI-2-deficient mice is independent of matriptase-mediated cleavage of EpCAM.Development (Cambridge, England) · 2023Article
- Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function.Biomedicines · 2023Review
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- EpCAM proteolysis and release of complexed claudin-7 repair and maintain the tight junction barrier.The Journal of cell biology · 2023Article
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- EPCAM and TROP2 share a role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice.Biology open · 2022Article
- Structural insights into theiScience · 2021Article
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- Trop2 Forms a Stable Dimer with Significant Structural Differences within the Membrane-Distal Region as Compared to EpCAM.International journal of molecular sciences · 2021Article
- Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.Human molecular genetics · 2021Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Congenital tufting enteropathy (CTE) is a severe autosomal recessive human diarrheal disorder with characteristic intestinal epithelial dysplasia. CTE can be caused by mutations in genes encoding EpCAM, a putative adhesion molecule, and HAI-2, a cell surface protease inhibitor. A similar phenotype occurs in mice whose intestinal epithelial cells (IECs) fail to express the tight junction-associated protein claudin-7. EpCAM stabilizes claudin-7 in IECs, and HAI-2 regulates the cell surface serine protease matriptase, a known modifier of intestinal epithelial physiology. Therefore, we hypothesized that HAI-2, matriptase, EpCAM, and claudin-7 were functionally linked. Herein we have demonstrated that active matriptase cleaves EpCAM after Arg80 and that loss of HAI-2 in IECs led to unrestrained matriptase activity and efficient cleavage of EpCAM. Cleavage of EpCAM decreased its ability to associate with claudin-7 and targeted it for internalization and lysosomal degradation in conjunction with claudin-7. CTE-associated HAI-2 mutant proteins exhibited reduced ability to inhibit matriptase and also failed to efficiently stabilize claudin-7 in IECs. These results identify EpCAM as a substrate of matriptase and link HAI-2, matriptase, EpCAM, and claudin-7 in a functionally important pathway that causes disease when it is dysregulated.
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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.