HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers
Over the last two decades, cell surface proteases belonging to the type II transmembrane serine protease (TTSP) family have emerged as important enzymes in the mammalian degradome, playing critical roles in epithelial biology, regulation of metabolic homeostasis, and cancer. Human airway trypsin-lik...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912027/ https://www.ncbi.nlm.nih.gov/pubmed/24498351 http://dx.doi.org/10.1371/journal.pone.0087675 |
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author | Miller, Gregory S. Zoratti, Gina L. Murray, Andrew S. Bergum, Christopher Tanabe, Lauren M. List, Karin |
author_facet | Miller, Gregory S. Zoratti, Gina L. Murray, Andrew S. Bergum, Christopher Tanabe, Lauren M. List, Karin |
author_sort | Miller, Gregory S. |
collection | PubMed |
description | Over the last two decades, cell surface proteases belonging to the type II transmembrane serine protease (TTSP) family have emerged as important enzymes in the mammalian degradome, playing critical roles in epithelial biology, regulation of metabolic homeostasis, and cancer. Human airway trypsin-like protease 5 (HATL5) is one of the few family members that remains uncharacterized. Here we demonstrate that HATL5 is a catalytically active serine protease that is inhibited by the two Kunitz type serine protease inhibitors, hepatocyte growth factor activator inhibitor (HAI)-1 and 2, as well as by serpinA1. Full-length HATL5 is localized on the cell surface of cultured mammalian cells as demonstrated by confocal microscopy. HATL5 displays a relatively restricted tissue expression profile, with both transcript and protein present in the cervix, esophagus, and oral cavity. Immunohistochemical analysis revealed an expression pattern where HATL5 is localized on the cell surface of differentiated epithelial cells in the stratified squamous epithelia of all three of these tissues. Interestingly, HATL5 is significantly decreased in cervical, esophageal, and head and neck carcinomas as compared to normal tissue. Analysis of cervical and esophageal cancer tissue arrays demonstrated that the squamous epithelial cells lose their expression of HATL5 protein upon malignant transformation. |
format | Online Article Text |
id | pubmed-3912027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39120272014-02-04 HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers Miller, Gregory S. Zoratti, Gina L. Murray, Andrew S. Bergum, Christopher Tanabe, Lauren M. List, Karin PLoS One Research Article Over the last two decades, cell surface proteases belonging to the type II transmembrane serine protease (TTSP) family have emerged as important enzymes in the mammalian degradome, playing critical roles in epithelial biology, regulation of metabolic homeostasis, and cancer. Human airway trypsin-like protease 5 (HATL5) is one of the few family members that remains uncharacterized. Here we demonstrate that HATL5 is a catalytically active serine protease that is inhibited by the two Kunitz type serine protease inhibitors, hepatocyte growth factor activator inhibitor (HAI)-1 and 2, as well as by serpinA1. Full-length HATL5 is localized on the cell surface of cultured mammalian cells as demonstrated by confocal microscopy. HATL5 displays a relatively restricted tissue expression profile, with both transcript and protein present in the cervix, esophagus, and oral cavity. Immunohistochemical analysis revealed an expression pattern where HATL5 is localized on the cell surface of differentiated epithelial cells in the stratified squamous epithelia of all three of these tissues. Interestingly, HATL5 is significantly decreased in cervical, esophageal, and head and neck carcinomas as compared to normal tissue. Analysis of cervical and esophageal cancer tissue arrays demonstrated that the squamous epithelial cells lose their expression of HATL5 protein upon malignant transformation. Public Library of Science 2014-02-03 /pmc/articles/PMC3912027/ /pubmed/24498351 http://dx.doi.org/10.1371/journal.pone.0087675 Text en © 2014 Miller et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Miller, Gregory S. Zoratti, Gina L. Murray, Andrew S. Bergum, Christopher Tanabe, Lauren M. List, Karin HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers |
title | HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers |
title_full | HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers |
title_fullStr | HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers |
title_full_unstemmed | HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers |
title_short | HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers |
title_sort | hatl5: a cell surface serine protease differentially expressed in epithelial cancers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912027/ https://www.ncbi.nlm.nih.gov/pubmed/24498351 http://dx.doi.org/10.1371/journal.pone.0087675 |
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