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-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.
Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Gregory S
GS
Miller
Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Gina L
GL
Zoratti
Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Andrew S
AS
Murray
Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Christopher
C
Bergum
Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Lauren M
LM
Tanabe
Department of Pharmacology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan ; Department of Oncology, Wayne State University School of Medicine and Barbara Ann Karmanos Cancer Institute, Detroit, Michigan.
Karin
K
List
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000201:enzymology / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics
D008565:Membrane Proteins; D012697:Serine Endopeptidases; C000593179:TMPRSS11b protein, human; C112256:human airway trypsin-like protease