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HATL5: a cell surface serine protease differentially expressed in epithelial cancers
Gregory S Miller1, Gina L Zoratti2, Andrew S Murray2
1Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Human airway trypsin-like protease 5 (HATL5) is a newly characterized cell surface protease. Its expression decreases in several cancers, suggesting a potential role in epithelial cell regulation and cancer development.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Type II transmembrane serine proteases (TTSPs) are crucial in mammalian biology.
- Many TTSPs are implicated in epithelial functions and cancer.
- Human airway trypsin-like protease 5 (HATL5) is an uncharacterized TTSP family member.
Purpose of the Study:
- To characterize the enzymatic activity, localization, and expression of HATL5.
- To investigate the role of HATL5 in epithelial tissues and cancer.
Main Methods:
- Enzyme activity assays and inhibition studies.
- Confocal microscopy for cell surface localization.
- Quantitative real-time PCR and immunohistochemistry for tissue expression analysis.
- Analysis of cancer tissue arrays.
Main Results:
- HATL5 is a catalytically active serine protease.
- HATL5 is inhibited by Kunitz-type inhibitors (HAI-1, HAI-2) and serpinA1.
- Full-length HATL5 localizes to the cell surface.
- HATL5 exhibits restricted expression in cervix, esophagus, and oral cavity epithelia.
- HATL5 expression is significantly reduced in cervical, esophageal, and head and neck carcinomas.
Conclusions:
- HATL5 is a functional cell surface protease.
- HATL5 expression is downregulated in various squamous cell carcinomas.
- HATL5 may function in maintaining epithelial homeostasis and suppressing tumorigenesis.
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