PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells

Introduction: PARK7/DJ-1 is an oncogene that is associated with tumorigenesis in many cancers. Recent studies have demonstrated the importance of DJ-1 in the origin and development of uveal melanoma (UM). We present an analysis of the role of the DJ-1 protein in UM cells, especially in its effect on...

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Published in:Tumori 2023-02, Vol.109 (1), p.47-53
Main Authors: Lago-Baameiro, Nerea, Santiago-Varela, Maria, Camino, Tamara, Silva-Rodríguez, Paula, Bande, Manuel, Blanco-Teijeiro, Maria Jose, Pardo, Maria, Piñeiro, Antonio
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Cell Proliferation
Humans
Protein Deglycase DJ-1 - genetics
Protein Deglycase DJ-1 - metabolism
Protein Deglycase DJ-1 - pharmacology
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction
Uveal Neoplasms - genetics
Uveal Neoplasms - metabolism
Uveal Neoplasms - pathology
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Summary:Introduction: PARK7/DJ-1 is an oncogene that is associated with tumorigenesis in many cancers. Recent studies have demonstrated the importance of DJ-1 in the origin and development of uveal melanoma (UM). We present an analysis of the role of the DJ-1 protein in UM cells, especially in its effect on proliferation and migration. Methods: UM cells from a primary tumor, Mel 270, and its liver metastasis, OMM2.5, were transfected with lentiviral-delivered shRNA against PARK7/DJ-1. Evaluation of cell migration and proliferation was performed using the xCELLigence real-time cell analyzer (RTCA). The effect of DJ-1 inhibition on the PTEN-Akt signaling pathway was also studied by immunoblotting. Results: The silencing of PARK7/DJ-1 oncoprotein expression produced a significant decrease of phosphorylated Akt (S473) in Mel270 and in metastatic OMM2.5 UM cells with no alteration on tumor suppressor PTEN expression. The diminution of PARK7/DJ-1 expression significantly inhibited real-time proliferation and invasion of Mel270 and OMM2.5 and the invasion potential of the metastatic cells. Conclusion: DJ-1 appears to play a key role on the PTEN/Akt pathway in UM. DJ-1 inhibition appears to have a negative effect on proliferation and invasion of UM cells. This suggests DJ-1 as a potential therapeutic target in UM.
ISSN:0300-8916
2038-2529
DOI:10.1177/03008916211061766