Prostasin regulates PD-L1 expression in human lung cancer cells.
Adenocarcinoma of Lung
/ enzymology
B7-H1 Antigen
/ genetics
Cell Line, Tumor
Epidermal Growth Factor
/ pharmacology
ErbB Receptors
/ genetics
Extracellular Vesicles
/ drug effects
Gene Expression Regulation, Neoplastic
Humans
Interferon-gamma
/ pharmacology
Lung Neoplasms
/ enzymology
Mitogen-Activated Protein Kinases
/ metabolism
Protein Kinase C
/ metabolism
Serine Endopeptidases
/ genetics
Signal Transduction
Up-Regulation
CD274
PRSS8
extracellular vesicles
immune checkpoint
interferon-gamma
Journal
Bioscience reports
ISSN: 1573-4935
Titre abrégé: Biosci Rep
Pays: England
ID NLM: 8102797
Informations de publication
Date de publication:
30 07 2021
30 07 2021
Historique:
received:
05
06
2021
revised:
18
06
2021
accepted:
25
06
2021
entrez:
9
7
2021
pubmed:
10
7
2021
medline:
1
2
2022
Statut:
ppublish
Résumé
The serine protease prostasin is a negative regulator of lipopolysaccharide-induced inflammation and has a role in the regulation of cellular immunity. Prostasin expression in cancer cells inhibits migration and metastasis, and reduces epithelial-mesenchymal transition. Programmed death-ligand 1 (PD-L1) is a negative regulator of the immune response and its expression in cancer cells interferes with immune surveillance. The aim of the present study was to investigate if prostasin regulates PD-L1 expression. We established sublines overexpressing various forms of prostasin as well as a subline deficient for the prostasin gene from the Calu-3 human lung cancer cells. We report here that PD-L1 expression induced by interferon-γ (IFNγ) is further enhanced in cells overexpressing the wildtype membrane-anchored prostasin. The PD-L1 protein was localized on the cell surface and released into the culture medium in extracellular vesicles (EVs) with the protease-active prostasin. The epidermal growth factor-epidermal growth factor receptor (EGF-EGFR), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK) participated in the prostasin-mediated up-regulation of PD-L1 expression. A Gene Set Enrichment Analysis (GSEA) of patient lung tumors in The Cancer Genome Atlas (TCGA) database revealed that prostasin and PD-L1 regulate common signaling pathways during tumorigenesis and tumor progression.
Identifiants
pubmed: 34240739
pii: 229226
doi: 10.1042/BSR20211370
pmc: PMC8273379
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
Epidermal Growth Factor
62229-50-9
Interferon-gamma
82115-62-6
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Protein Kinase C
EC 2.7.11.13
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Serine Endopeptidases
EC 3.4.21.-
prostasin
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 The Author(s).
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