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Tumour promoting and suppressing roles of the atypical MAP kinase signalling pathway ERK3/4-MK5

Sergiy Kostenko1, Gianina Dumitriu, Ugo Moens

  • 1Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, NO-9037, Norway. ugo.moens@uit.no.

Journal of Molecular Signaling
|July 18, 2012
PubMed

Insights

The atypical mitogen-activated protein (MAP) kinase pathway ERK3/4-MK5 shows dual roles in cancer, acting as both anti-oncogenic and pro-oncogenic. This review explores its mutations, expression, and mechanisms in tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Signal Transduction

Background:

  • Signal transduction pathways, particularly mitogen-activated protein (MAP) kinase pathways, are crucial in cancer development.
  • While typical MAP kinase pathways (ERK1/2, p38MAPK, JNK) are well-studied, the atypical ERK3/4-MK5 pathway's role in tumorigenesis is emerging.
  • The ERK3/4-MK5 pathway exhibits context-dependent anti-oncogenic and pro-oncogenic properties.

Purpose of the Study:

  • To review mutations in ERK3, ERK4, and MK5 genes found in various cancers.
  • To report aberrant expression levels of ERK3, ERK4, and MK5 proteins in human tumors.
  • To discuss the mechanisms through which the ERK3/4-MK5 pathway influences cancer progression, including senescence, angiogenesis, and invasiveness.

Main Methods:

  • Literature review of genetic mutations and protein expression studies.
  • Analysis of existing data on the functional roles of the ERK3/4-MK5 pathway in cancer models.
  • Synthesis of information on the mechanistic links between the pathway and cancer hallmarks.

Main Results:

  • Mutations in genes encoding ERK3, ERK4, and MK5 have been identified across different cancer types.
  • Aberrant expression levels of these proteins are observed in human tumors, suggesting their involvement in oncogenesis.
  • The ERK3/4-MK5 pathway has been implicated in inducing cellular senescence, promoting angiogenesis, and enhancing tumor invasiveness.

Conclusions:

  • The atypical MAP kinase pathway ERK3/4-MK5 plays a complex role in cancer, with both tumor-suppressive and tumor-promoting functions.
  • Understanding the mutations and expression patterns of ERK3, ERK4, and MK5 is vital for cancer research.
  • Further investigation into the mechanisms of the ERK3/4-MK5 pathway could reveal novel therapeutic targets for cancer treatment.

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