RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate promotile/invasive gene program and phenotype in epithelial cells (Mol Cell, 2009, 35:511-522)

報告日期: 2010/03/23
報告時間: 15:10/16:00
報告學生: 林秀冠(英文報告)
講評老師: 劉校生

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 35, 511–522, August 28, 2009


Speaker : Hsiu-Kuan Lin (林秀冠)

Commentator : Hsiao-Sheng Liu (劉校生老師)

Date : 2010-03-23() 15:10-16:00

Room : 602


Epithelial-mesenchymal transition (EMT) is a biologic process that allows a polarized epithelial cell to down-regulate its epithelial phenotype and undergo transformation to a mesenchymal cell phenotype, which includes enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, and greatly increased production of ECM components. EMT exists as three distinct subtypes which played important roles during development, tissue regeneration, and carcinoma progression(1). Accumulated studies showed that the growth factor-activated and RAS-dependent MAPK cascade composed of RAF, MEK, and the effector kinase ERK is a major signaling pathway to induce mesenchymal motility and invasiveness in epithelial cells(2). However, while ERK is crucial for these processes, the mechanism by which ERK controls motile and invasive capacities of epithelial cells remain elusive. In this study, the authors first demonstrate ERK-activated kinase RSK (ribosomal S6 kinase) is required to induce mesenchymal motility and invasive capacities in nontransformed epithelial and carcinoma cells. Overexpression of RSK is sufficient to induce motile response. To elucidate how RSK regulates motility and invasion, they checked the RSK-regulated mRNA expression profiling. The data revealed that a major role of RSK was to activate a coordinate promotile and proinvasive gene program, such as laminin 332, uPA and uPAR, Flt-1, MMP-1, α2 integrin, MMP-9 and CD44, MMP-10, MMP-13, α-actinin-1 and -4, RhoC, etc.. Such program suggested RSK might coordinately modulate the extracellular environment, intracellular motility apparatus, and receptors mediating communication between these compartments to stimulate motility and invasion. Authors further demonstrated that RSK regulate the motility/invasive gene program by FRA1-dependent and –independent mechanisms. In conclusion, this study reveals a mechanism whereby the RAS-ERK pathway induces motile and invasive capacities in epithelial cells by identifying RSK as a key effector. Via the action of RSK, multiple yet highly coordinate transcription-dependent mechanisms for stimulation of motility and invasiveness were initiated.


1.   Kalluri R, and Weinberg RA. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119:1420–1428 (2009).

2.   Grű nert, S., Jechlinger, M., and Beug, H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat. Rev. Mol. Cell Biol. 4, 657–665 (2003).