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Cancer Cell. 2007 May;11(5):447-60.

Rewired ERK-JNK signaling pathways in melanoma.

Author information

1
Signal Transduction Program, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA.

Abstract

Constitutive activation of MEK-ERK signaling is often found in melanomas. Here, we identify a mechanism that links ERK with JNK signaling in human melanoma. Constitutively active ERK increases c-Jun transcription and stability, which are mediated by CREB and GSK3, respectively. Subsequently, c-Jun increases transcription of target genes, including RACK1, an adaptor protein that enables PKC to phosphorylate and enhance JNK activity, enforcing a feed-forward mechanism of the JNK-Jun pathway. Activated c-Jun is also responsible for elevated cyclin D1 expression, which is frequently overexpressed in human melanoma. Our data reveal that, in human melanoma, the rewired ERK signaling pathway upregulates JNK and activates the c-Jun oncogene and its downstream targets, including RACK1 and cyclin D1.

PMID:
17482134
PMCID:
PMC1978100
DOI:
10.1016/j.ccr.2007.03.009
[Indexed for MEDLINE]
Free PMC Article
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