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...

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Autores principales: Miller, Gregory S., Zoratti, Gina L., Murray, Andrew S., Bergum, Christopher, Tanabe, Lauren M., List, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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.
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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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