Reference - Detail
| RRC ID | 54458 |
|---|---|
| Author | Sun Y, Zhang D, Guo X, Li W, Li C, Luo J, Zhou M, Xue L. |
| Title | MKK3 modulates JNK-dependent cell migration and invasion. |
| Journal | Cell Death Dis |
| Abstract |
The c-Jun N-terminal kinase (JNK) pathway plays essential roles in regulating a variety of physiological processes including cell migration and invasion. To identify critical factors that regulate JNK-dependent cell migration, we carried out a genetic screen in Drosophila based on the loss-of-cell polarity-triggered cell migration in the wing epithelia, and identified MKK3 licorne (lic) as an essential regulator of JNK-mediated cell migration and invasion. We found that loss of lic suppressed ptc > scrib-IR or ptc > Egr triggered cell migration in the wing epithelia, and Rasv12/lgl-/- induced tumor invasion in the eye discs. In addition, ectopic expression of Lic is sufficient to induce JNK-mediated but p38-independent cell migration, and cooperate with oncogenic Ras to promote tumor invasion. Consistently, Lic is able to activate JNK signaling by phosphorylating JNK, which up-regulates the matrix metalloproteinase MMP1 and integrin, characteristics of epithelial-mesenchymal transition (EMT). Moreover, lic is required for physiological JNK-mediate cell migration in thorax development. Finally, expression of human MKK3 in Drosophila is able to initiate JNK-mediated cell migration, cooperates with oncogenic Ras to trigger tumor invasion, and rescue loss-of-lic induced thorax closure defect. As previous studies suggest that MKK3 specifically phosphorylates and activates p38MAPK, our data provide the first in vivo evidence that MKK3 regulates JNK-dependent cell migration and invasion, a process evolutionarily conserved from flies to human. |
| Volume | 10(3) |
| Pages | 149 |
| Published | 2019-2-15 |
| DOI | 10.1038/s41419-019-1350-6 |
| PII | 10.1038/s41419-019-1350-6 |
| PMID | 30770795 |
| PMC | PMC6377636 |
| MeSH | Animals Animals, Genetically Modified Cell Movement / genetics* Cell Polarity / genetics Disease Models, Animal Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Epithelial-Mesenchymal Transition / genetics Evolution, Molecular Gene Knockdown Techniques HEK293 Cells Humans Integrin beta Chains / metabolism JNK Mitogen-Activated Protein Kinases / metabolism* MAP Kinase Kinase 3 / genetics MAP Kinase Kinase 3 / metabolism* MAP Kinase Signaling System / genetics* Matrix Metalloproteinase 1 / metabolism Neoplasm Invasiveness / genetics Protein Kinases / genetics Protein Kinases / metabolism* |
| IF | 5.959 |
| Times Cited | 2 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | 1388R-2 |