RSK Is a Principal Effector of the RAS-ERK Pathway for Eliciting a Coordinate Promotile/Invasive Gene Program and Phenotype in Epithelial Cells

Ulrik Doehn, Camilla Hauge, Scott R. Frank, Claus J. Jensen, Katarzyna Duda, Jakob V. Nielsen, Michael S Cohen, Jens V. Johansen, Benny R. Winther, Leif Lund, Ole Winther, Jack Taunton, Steen H. Hansen, Morten Froedin

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The RAS-stimulated RAF-MEK-ERK pathway confers epithelial cells with critical motile and invasive capacities during development, tissue regeneration, and carcinoma progression, often via promoting the epithelial-mesenchymal transition (EMT). Many mechanisms by which ERK exerts this control remain elusive. We demonstrate that the ERK-activated kinase RSK is necessary to induce mesenchymal motility and invasive capacities in nontransformed epithelial and carcinoma cells. RSK is sufficient to induce certain motile responses. Expression profiling analysis revealed that a primary role of RSK is to induce transcription of a potent promotile/invasive gene program by FRA1-dependent and -independent mechanisms. The program enables RSK to coordinately modulate the extracellular environment, the intracellular motility apparatus, and receptors mediating communication between these compartments to stimulate motility and invasion. These findings uncover a mechanism whereby the RAS-ERK pathway controls epithelial cell motility by identifying RSK as a key effector, from which emanate multiple highly coordinate transcription-dependent mechanisms for stimulation of motility and invasive properties.
Original languageEnglish
JournalMolecular Cell
Volume35
Issue number4
Pages (from-to)511-522
ISSN1097-2765
DOIs
Publication statusPublished - 2009
Externally publishedYes

Cite this