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CD40 Cross-Linking Induces Migration of Renal Tumor Cell through Nuclear Factor of Activated T Cells (NFAT) Activation
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 8871, p 8871 (2021), International Journal of Molecular Sciences, Volume 22, Issue 16
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin β1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC.
- Subjects :
- Male
MAPK/ERK pathway
cell migration
Cell
Apoptosis
urologic and male genital diseases
Cell Movement
Tumor Cells, Cultured
CD40/CD40L crosslinking
Neoplasm Metastasis
Biology (General)
Spectroscopy
biology
Chemistry
Kinase
NFATs
NFAT
Cell migration
General Medicine
Middle Aged
Prognosis
Kidney Neoplasms
female genital diseases and pregnancy complications
Computer Science Applications
Gene Expression Regulation, Neoplastic
Cross-Linking Reagents
medicine.anatomical_structure
Female
Intracellular
integrin β1
renal cell carcinoma
QH301-705.5
CD40 Ligand
Article
Catalysis
Inorganic Chemistry
Biomarkers, Tumor
medicine
Humans
CD40 Antigens
Physical and Theoretical Chemistry
Molecular Biology
Transcription factor
QD1-999
Aged
Cell Proliferation
CD40
NFATC Transcription Factors
Organic Chemistry
Cancer research
biology.protein
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 22
- Issue :
- 8871
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....48811df67733b3270ea8992e08888109