NFATc2 is a potential therapeutic target in human melanoma

Perotti, Valentina, Baldassari, Paola, Bersani, Ilaria, Molla, Alessandra, Vegetti, Claudia, Tassi, Elena, Dal Col, Jessica, Dolcetti, Riccardo, Anichini, Andrea and Mortarini, Roberta (2012) NFATc2 is a potential therapeutic target in human melanoma. Journal of Investigative Dermatology, 132 11: 2652-2660. doi:10.1038/jid.2012.179

Author Perotti, Valentina
Baldassari, Paola
Bersani, Ilaria
Molla, Alessandra
Vegetti, Claudia
Tassi, Elena
Dal Col, Jessica
Dolcetti, Riccardo
Anichini, Andrea
Mortarini, Roberta
Title NFATc2 is a potential therapeutic target in human melanoma
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
Publication date 2012-11-01
Year available 2012
Sub-type Article (original research)
DOI 10.1038/jid.2012.179
Open Access Status Not yet assessed
Volume 132
Issue 11
Start page 2652
End page 2660
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
The identification of intracellular signaling pathways that promote cell proliferation and resistance to cell death may lead to the development of improved treatment for advanced melanoma. Here we show that the calcineurin/nuclear factor of activated T cells c2 (NFATc2) pathway has an antiapoptotic role in melanoma cells. Expression of NFATc2 was constitutive in vitro and in vivo in human melanoma, and cyclosporin A (CsA) treatment of melanoma cells led to downmodulation of NFATc2. Inhibition of the calcineurin/NFAT pathway by CsA, or by NFATc2 silencing, led to modulation of cell cycle inhibitors and apoptosis-related proteins such as Apollon, and promoted caspase-dependent apoptosis of neoplastic cells. Calcineurin/NFATc2 targeting significantly enhanced melanoma cell death induced by antitumor agents, such as MEK- or BRAFV600E-specific inhibitors, and tumor necrosis factor-related apoptosis-inducing ligand, which trigger the intrinsic or extrinsic pathway of apoptosis, respectively. These findings identify NFATc2 as a potential therapeutic target in melanoma.
Keyword Dermatology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 9998
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 22 times in Scopus Article | Citations
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