The regulatory roles of ROCK and MRCK kinases in the plasticity of cancer cell migration

Cancer Lett. 2015 Jun 1;361(2):185-96. doi: 10.1016/j.canlet.2015.03.017. Epub 2015 Mar 18.

Abstract

Metastatic cancer cells show great plasticity in their migratory mechanisms. In this review we briefly describe the signal transduction pathways associated with the ROCK and MRCK kinases and their roles in cancer cell migration and in its plasticity. With respect to therapeutic strategies targeting metastatic cancers, selectively blocking a single target, such as ROCK or MRCK, can induce alternate modes of cancer cell migration (i.e. plasticity) making the treatment ineffective. To address the problem of plasticity, we will discuss the strategy of simultaneous targeting of both ROCK and MRCK as an effective anti-metastatic therapeutics.

Keywords: Anticancer therapeutics; Cell migration plasticity; MRCK; Polypharmacology; ROCK and MRCK inhibitors; Rho kinase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Movement / physiology*
  • Humans
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases