Ribosomal Protein S6 Kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein
2011

RSK-2's Role in Cancer Cell Transition

publication Evidence: high

Author Information

Author(s): Ma Qi, Guin Sunny, Padhye Snehal S, Zhou Yong-Qing, Zhang Rui-Wen, Wang Ming-Hai

Primary Institution: Division of Cancer Biology at State Key Laboratory for Diagnosis & Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China

Hypothesis

The study aims to identify the major signaling molecule(s) responsible for epithelial to mesenchymal transition (EMT) induced by macrophage-stimulating protein (MSP).

Conclusion

RSK2 activation is a critical determinant linking RON signaling to cellular EMT, and inhibiting RSK2 may provide a therapeutic opportunity for blocking cancer cell migration and invasion.

Supporting Evidence

  • MSP stimulation dissociated RSK2 from Erk1/2 and promoted RSK2 nuclear translocation.
  • Specific RSK inhibitor SL0101 completely prevented MSP-induced RSK phosphorylation.
  • Forced RSK2 expression in HT-29 cancer cells resulted in an EMT-like phenotype upon MSP stimulation.
  • Silencing RSK2 in pancreatic cancer cells significantly inhibited MSP-induced EMT-like phenotype and cell migration.

Takeaway

This study found that a protein called RSK2 helps cancer cells change shape and become more mobile, which can make them spread more easily in the body.

Methodology

The study used MDCK cells expressing RON and various small chemical inhibitors to identify RSK2's role in MSP-induced EMT.

Digital Object Identifier (DOI)

10.1186/1476-4598-10-66

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