Tumor-Intrinsic PD-L1 Exerts an Oncogenic Function through the Activation of the Wnt/β-Catenin Pathway in Human Non-Small Cell Lung Cancer.
NSCLC
PD-L1
Wnt/β-catenin pathway
exosomal miRNA
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
20 Sep 2022
20 Sep 2022
Historique:
received:
10
05
2022
revised:
05
09
2022
accepted:
13
09
2022
entrez:
14
10
2022
pubmed:
15
10
2022
medline:
18
10
2022
Statut:
epublish
Résumé
Programmed death ligand 1 (PD-L1) strongly inhibits T cell activation, thereby aiding tumors in escaping the immune response. PD-L1 inhibitors have proven to be effective in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). Yet, the knowledge regarding the biological function of tumor-intrinsic PD-L1 in lung cancer remains obscure. In our study, we set the goal of determining the function of PD-L1 using overexpression and knockdown strategies. PD-L1 silencing resulted in decreased migratory and invasive ability of tumor cells, together with attenuated colony-forming capacity. Ectopic expression of PD-L1 showed the opposite effects, along with increased activities of MAPK and Wnt/β-catenin pathways, and the upregulation of Wnt/β-catenin target genes. Additionally, overexpression of PD-L1 was associated with dysregulated cellular and exosomal miRNAs involved in tumor progression and metastasis. In primary lung tumors, immunohistochemistry revealed that both PD1 and PD-L1 were highly expressed in squamous cell carcinoma (SCC) compared to adenocarcinoma (
Identifiants
pubmed: 36232331
pii: ijms231911031
doi: 10.3390/ijms231911031
pmc: PMC9569632
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
Immune Checkpoint Inhibitors
0
MicroRNAs
0
beta Catenin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : University Hospital Jena IZKF
ID : IZKF-MSP-06
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