Co-Crystal Structures of Inhibitors with MRCKβ, a Key Regulator of Tumor Cell Invasion
2011

Inhibitors of MRCKβ and ROCK in Cancer Cell Invasion

Sample size: 3 publication 10 minutes Evidence: high

Author Information

Author(s): Heikkila Timo, Wheatley Edward, Crighton Diane, Schroder Ewald, Boakes Alexandra, Kaye Sarah J., Mezna Mokdad, Pang Leon, Rushbrooke Mathew, Turnbull Andrew, Olson Michael F.

Primary Institution: Cancer Research Technology Discovery Laboratories, Wolfson Institute for Biomedical Research, London, United Kingdom

Hypothesis

The combined inhibition of MRCKα and MRCKβ along with ROCK kinases will significantly reduce cancer cell invasion.

Conclusion

The study found that combined inhibition of MRCK and ROCK significantly reduces the invasion of cancer cells in a 3D matrix.

Supporting Evidence

  • Combined MRCK and ROCK inhibition significantly reduced cancer cell invasion in 3D assays.
  • 11 compounds were identified that inhibited MRCKβ activity by over 80%.
  • The study provides structural insights into MRCKβ that can aid in drug development.

Takeaway

Researchers found that blocking two proteins, MRCK and ROCK, together helps stop cancer cells from moving and spreading.

Methodology

The study used 3D matrix invasion assays and siRNA knockdown techniques to assess the effects of MRCK and ROCK inhibition on cancer cell invasion.

Potential Biases

Potential bias due to the use of specific inhibitors that may also affect other kinases.

Limitations

The study may have off-target effects due to the use of siRNA and inhibitors that are not specific to MRCK.

Participant Demographics

The study focused on MDA MB 231 breast cancer cells.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0024825

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