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An siRNA screen identifies RSK1 as a key modulator of lung cancer metastasis

R Lara1, F A Mauri, H Taylor

  • 1Department of Oncology, Hammersmith Campus, Cyclotron Building, London, UK.

Oncogene
|March 23, 2011
PubMed

Insights

Ribosomal S6 kinase 1 (RSK1) loss enhances lung cancer cell migration and metastasis. RSK1 interacts with actin regulators and its reduced levels in tumors correlate with increased metastases, suggesting RSK1 as a potential biomarker.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Cell migration is crucial for cancer metastasis.
  • Kinases play significant roles in regulating cell motility.
  • Identifying key kinases involved in lung cancer progression is essential for therapeutic development.

Purpose of the Study:

  • To identify kinases that regulate lung cancer cell migration and invasion.
  • To investigate the role of ribosomal S6 kinase 1 (RSK1) in lung cancer metastasis.
  • To explore RSK1's interaction with cellular components and its clinical relevance.

Main Methods:

  • Kinome-wide siRNA screening in A549 lung cancer cells.
  • Collagen-based 3D invasion assays.
  • Bioinformatic analysis and co-immunoprecipitation for protein interactions.
  • In vivo metastasis assays using a zebrafish model.
  • Analysis of RSK1 expression in human lung cancer tissues.

Main Results:

  • A screen identified 70 kinases affecting cell migration, with RSK1 silencing increasing motility.
  • RSK1 interacts with actin regulators VASP and Mena, and phosphorylates VASP at T278.
  • RSK1 silencing enhanced lung cancer cell metastatic potential in vivo.
  • Reduced RSK1 levels in metastatic lung cancer lesions and RSK1-negative tumors correlated with increased metastases.

Conclusions:

  • RSK1 plays a critical role in regulating lung cancer cell migration and metastasis.
  • RSK1's interaction with VASP and Mena is a key mechanism for its function.
  • RSK1 is a potential biomarker for lung cancer metastasis and a therapeutic target.

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