ERK and RSK regulate distinct steps of a cellular program that induces transition from multicellular epithelium to single cell phenotype
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24012955
DOI
10.1016/j.cellsig.2013.08.024
PII: S0898-6568(13)00259-3
Knihovny.cz E-resources
- Keywords
- 4-hydroxytamoxifen, 4HT, ALLM, ALLN, Calpain, Cell–cell junctions, EMT, ER, MAPK/ERK, MDCK, Madin–Darby Canine Kidney, Migration, N-Acetyl-l-leucine-l-leucine-l-norleucinal, N-Acetyl-l-leucyl-l-leucyl-l-methional, Polarity, RSK, epithelial–mesenchymal transition, ligand binding domain of estrogen receptor,
- MeSH
- Cell Line MeSH
- Epithelial Cells cytology metabolism MeSH
- Extracellular Signal-Regulated MAP Kinases metabolism MeSH
- Cadherins metabolism MeSH
- Calpain metabolism MeSH
- Ribosomal Protein S6 Kinases, 90-kDa metabolism MeSH
- Humans MeSH
- MAP Kinase Signaling System MeSH
- Intercellular Junctions metabolism MeSH
- Cell Movement MeSH
- Cell Polarity MeSH
- Dogs MeSH
- Signal Transduction * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Dogs MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Extracellular Signal-Regulated MAP Kinases MeSH
- Cadherins MeSH
- Calpain MeSH
- Ribosomal Protein S6 Kinases, 90-kDa MeSH
The ERK (extracellular signal-regulated kinases) cascade has an evolutionarily conserved three tier architecture consisting of protein kinases Raf, MEK (MAPK/ERK kinase) and ERK. Following activation, ERK phosphorylates various cellular elements leading to diverse cellular responses. Downstream of ERK the family of p90 ribosomal S6 kinases (RSKs) has been proven to be an important conveyor of ERK signaling, however, little is known if ERK and RSK coordinate their functions to generate a specific biological response. Here we show that in epithelial cells conditional activation of the ERK pathway causes phenotypic conversion of epithelial cells to autonomously migrating cells. This process involves two sequential steps characterized by loss of apical-basal polarity followed by cell scattering. The activation of ERK, but not RSK, is sufficient for the execution of the first step and it requires calpain mediated remodeling of actin cytoskeleton. Conversely, RSK regulates the successive stage characterized by cell-cell contact weakening and increased cellular migration. Thus, ERK and RSK regulate different cellular subprograms and coordinated execution of these subprograms in time generates a relevant biological response. Our data also suggest that the mechanism by which the ERK pathway controls a cellular response may be distributed between ERK and RSK, rather than being elicited by a single effector kinase.
References provided by Crossref.org
Anti-angiogenic effects of the blue-green alga Arthrospira platensis on pancreatic cancer
Cell polarity signaling in the plasticity of cancer cell invasiveness
