Rewired ERK-JNK Signaling Pathways in Melanoma

Pablo Lopez-Bergami, Conway Huang, James S. Goydos, Dana Yip, Menashe Bar-Eli, Meenhard Herlyn, Keiran S.M. Smalley, Alka Mahale, Alexey Eroshkin, Stuart Aaronson, Ze'ev Ronai

Research output: Contribution to journalArticlepeer-review

242 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)447-460
Number of pages14
JournalCancer Cell
Volume11
Issue number5
DOIs
StatePublished - May 8 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

Keywords

  • SIGNALING

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