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 this study was to investigate if prostasin regulates PD-L1 expression. We established sublines over-expressing 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-gamma (IFNg) is further enhanced in cells over-expressing the wild-type 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.
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Research Article|
June 28 2021
Prostasin regulates PD-L1 expression in human lung cancer cells
Li-Mei Chen;
University of Central Florida Burnett School of Biomedical Sciences, Orlando, Florida, United States
* Corresponding Author; email: Limei.Chen@ucf.edu
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Julius C Chai;
Julius C Chai
University of Central Florida Burnett School of Biomedical Sciences, Orlando, Florida, United States
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Bin Liu;
Bin Liu
The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States
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Tara M Strutt;
Tara M Strutt
University of Central Florida Burnett School of Biomedical Sciences, Orlando, Florida, United States
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K Kai McKinstry;
K Kai McKinstry
University of Central Florida Burnett School of Biomedical Sciences, Orlando, Florida, United States
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Karl X Chai
Karl X Chai
University of Central Florida Burnett School of Biomedical Sciences, Orlando, Florida, United States
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Publisher: Portland Press Ltd
Received:
June 04 2021
Revision Received:
June 18 2021
Accepted:
June 25 2021
Online ISSN: 1573-4935
Print ISSN: 0144-8463
Copyright 2021 The Author(s)
2021
This is an Accepted Manuscript; not the final Version of Record. You are encouraged to use the final Version of Record that, when published, will replace this manuscript and be freely available under a Creative Commons licence.
Biosci Rep (2021) BSR20211370.
Article history
Received:
June 04 2021
Revision Received:
June 18 2021
Accepted:
June 25 2021
Citation
Li-Mei Chen, Julius C Chai, Bin Liu, Tara M Strutt, K Kai McKinstry, Karl X Chai; Prostasin regulates PD-L1 expression in human lung cancer cells. Biosci Rep 2021; BSR20211370. doi: https://doi.org/10.1042/BCJ20210407
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