dc.contributor.author |
Szabó, Attila |
|
dc.contributor.author |
Fekete, Tünde |
|
dc.contributor.author |
Koncz, Gábor |
|
dc.contributor.author |
Kumar BV |
|
dc.contributor.author |
Pázmándi, Kitti Linda |
|
dc.contributor.author |
Foldvari Z |
|
dc.contributor.author |
Hegedűs, Balázs |
|
dc.contributor.author |
Garay, Tamás |
|
dc.contributor.author |
Bácsi, Attila |
|
dc.contributor.author |
Rajnavölgyi, Éva |
|
dc.contributor.author |
Lányi, Árpád |
|
dc.date.accessioned |
2016-09-20T10:17:31Z |
|
dc.date.available |
2016-09-20T10:17:31Z |
|
dc.date.issued |
2016 |
|
dc.identifier.citation |
pagination=335-347;
journalVolume=28;
journalIssueNumber=5;
journalTitle=CELLULAR SIGNALLING; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/3480 |
|
dc.identifier.uri |
doi:10.1016/j.cellsig.2016.01.012 |
|
dc.description.abstract |
BACKGROUND: BRAF-mutant melanoma is characterized by aggressive metastatic potential and therapeutic resistance. The innate immune receptor RIG-I has emerged as a potential target in melanoma therapies but the contributing pathways involved in anti-cancer activity are poorly characterized. METHODS: Baseline and ATRA-induced expression of RIG-I in nine (3 wild type and 6 BRAF-mutant) melanoma cell lines was measured with Q-PCR and Western blot. Ligand-specific stimulation of RIG-I was detected by Q-PCR and ELISA. Activation of the RIG-I-coupled IRF3, NF-kappaB and MAPK pathways was tested with protein array and Western blot. Cell proliferation and apoptosis was monitored by flow cytometry and cell counting. Down modulation of MKP-1 expression in melanoma cells was performed by specific siRNA. RESULTS: Short-term ATRA pre-treatment increases the expression of RIG-I in BRAF-mutant melanoma cells. Specific activation of RIG-I by 5'ppp-dsRNA leads to increased activity of the IRF3-IFNbeta pathway but does not influence NF-kappaB signaling. RIG-I mediates the targeted dephosphorylation of several MAPKs (p38, RSK1, GSK-3alpha/beta, HSP27) via the endogenous regulator MKP-1 resulting in decreased melanoma cell proliferation. CONCLUSION: RIG-I has the potential to exert anticancer activity in BRAF-mutant melanoma via controlling IFNbeta production and MAPK signaling. This is the first study showing that RIG-I activation results in MKP-1-mediated inhibition of cell proliferation via controlling the p38-HSP27, c-Jun and rpS6 pathways thus identifying RIG-I and MKP-1 as novel and promising therapeutical targets. |
|
dc.relation.ispartof |
urn:issn:0898-6568 |
|
dc.title |
RIG-I inhibits the MAPK-dependent proliferation of BRAF mutant melanoma cells via MKP-1. |
|
dc.type |
Journal Article |
|
dc.date.updated |
2016-06-09T09:34:03Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
3016076 |
|
dc.identifier.wos |
000372679900001 |
|
dc.identifier.pubmed |
26829212 |
|
dc.contributor.department |
SE/AOK/I/IISZPI/MTA-SE Molekuláris Onkológia Kutatócsoport |
|
dc.contributor.department |
SE/AOK/I/II. Sz. Patológiai Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|