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 Cohen, Jens V. Johansen, Benny R. Winther, Leif R. Lund, Ole Winther, Jack Taunton, Steen H. Hansen, Morten Frödin

Research output: Contribution to journalArticle

137 Citations (Scopus)

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 (US)
Pages (from-to)511-522
Number of pages12
JournalMolecular Cell
Volume35
Issue number4
DOIs
StatePublished - Aug 28 2009
Externally publishedYes

Fingerprint

MAP Kinase Signaling System
Epithelial Cells
Phenotype
Genes
Carcinoma
Epithelial-Mesenchymal Transition
Cell Movement
Regeneration
Phosphotransferases

Keywords

  • CELLCYCLE
  • DNA
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

RSK Is a Principal Effector of the RAS-ERK Pathway for Eliciting a Coordinate Promotile/Invasive Gene Program and Phenotype in Epithelial Cells. / Doehn, Ulrik; Hauge, Camilla; Frank, Scott R.; Jensen, Claus J.; Duda, Katarzyna; Nielsen, Jakob V.; Cohen, Michael; Johansen, Jens V.; Winther, Benny R.; Lund, Leif R.; Winther, Ole; Taunton, Jack; Hansen, Steen H.; Frödin, Morten.

In: Molecular Cell, Vol. 35, No. 4, 28.08.2009, p. 511-522.

Research output: Contribution to journalArticle

Doehn, U, Hauge, C, Frank, SR, Jensen, CJ, Duda, K, Nielsen, JV, Cohen, M, Johansen, JV, Winther, BR, Lund, LR, Winther, O, Taunton, J, Hansen, SH & Frödin, M 2009, 'RSK Is a Principal Effector of the RAS-ERK Pathway for Eliciting a Coordinate Promotile/Invasive Gene Program and Phenotype in Epithelial Cells', Molecular Cell, vol. 35, no. 4, pp. 511-522. https://doi.org/10.1016/j.molcel.2009.08.002
Doehn, Ulrik ; Hauge, Camilla ; Frank, Scott R. ; Jensen, Claus J. ; Duda, Katarzyna ; Nielsen, Jakob V. ; Cohen, Michael ; Johansen, Jens V. ; Winther, Benny R. ; Lund, Leif R. ; Winther, Ole ; Taunton, Jack ; Hansen, Steen H. ; Frödin, Morten. / RSK Is a Principal Effector of the RAS-ERK Pathway for Eliciting a Coordinate Promotile/Invasive Gene Program and Phenotype in Epithelial Cells. In: Molecular Cell. 2009 ; Vol. 35, No. 4. pp. 511-522.
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