ReviewInternational journal of molecular sciences2026
Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.
Review in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- The role of HAI-1 in urothelial bladder cancer: Tissue expression, ectodomain shedding and clinical outcomes.Biochemistry and biophysics reports · 2026Article
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.
Funding
Abstract
Pericellular proteolysis is essential for maintaining tissue homeostasis. Central to this process are hepatocyte growth factor activator inhibitor-1 (HAI-1) and HAI-2, membrane-bound inhibitors that regulate type II transmembrane serine proteases, including matriptase and prostasin, through high-affinity Kunitz domains. This review summarizes current understanding of their molecular structures, physiological roles, and cancer-related clinical relevance. Genetic models reveal HAI-1 is critical for placental and skin development, while HAI-2 is crucial for neural tube closure and intestinal integrity. In cancer, HAIs generally act as tumor suppressors. Their downregulation, often via promoter hypermethylation, leads to excessive activation of hepatocyte growth factor/c-MET or protease-activated receptor-2/NF-κB signaling, promoting epithelial-mesenchymal transition and cancer progression. Clinically, reduced HAI levels in tumors correlate with metastasis and poor prognosis in several carcinomas. Paradoxically, elevated HAI expression in certain cancers suggests context-dependent pro-tumor functions. Emerging evidence links HAI loss to immune suppression, notably via M2 macrophage polarization in lung cancer. Finally, we highlight future directions for identifying tissue-specific serine proteases, downstream signaling, and therapeutic strategies, including recombinant mimetics and epigenetic reactivation, in precision oncology. In conclusion, HAI-1 and HAI-2 are key regulators of tissue homeostasis and cancer, with overlapping yet distinct functions, which present promising opportunities for therapeutic targeting.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.