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Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Updated: Jun 17, 2026

The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions
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Phenotype-assisted transcriptome analysis identifies FOXM1 downstream from Ras-MKK3-p38 to regulate in vitro cellular

A Behren1, S Mühlen, G A Acuna Sanhueza

  • 1Cancer Vaccine, Ludwig Institute for Cancer Research Ltd, Melbourne Centre for Clinical Sciences, Heidelberg, VIC, Australia.

Oncogene
|December 22, 2009
PubMed
Summary
This summary is machine-generated.

The Ras oncogene pathway activates p38, promoting cell invasion. Researchers identified FOXM1 as a key target, crucial for Ras and MKK3-induced invasion and growth in NIH3T3 fibroblasts.

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Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • The Ras oncogene activates multiple MAPK pathways, including ERK, JNK, and p38.
  • The Ras-MKK3-p38 signaling cascade mediates cellular phenotypes such as apoptosis and invasion.

Purpose of the Study:

  • To identify molecular targets of the Ras-MKK3-p38 pathway that specifically regulate cellular invasion.
  • To understand the downstream effectors governing invasive phenotypes induced by Ras activation.

Main Methods:

  • Stable transfection of NIH3T3 fibroblasts with MKK3(act) cDNA.
  • In vitro invasion assays to isolate highly invasive cells.
  • Genome-wide transcriptome analysis and protein-interaction network analysis.
  • FOXM1 RNA-knockdown experiments.

Main Results:

  • MKK3(act) transfection induced p38-dependent invasiveness and anchorage-independent growth in NIH3T3 cells.
  • Transcriptome analysis identified FOXM1, PLK1, and CDK1 as differentially regulated in invasive cells.
  • FOXM1 knockdown inhibited invasion and anchorage-independent growth in Ras- and MKK3-activated cells.

Conclusions:

  • FOXM1 is a critical downstream target of the Ras-MKK3-p38 pathway.
  • FOXM1 plays a key role in mediating Ras- and MKK3-induced cellular invasion and anchorage-independent growth.