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ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and

Anne von Thun1, Marc Birtwistle, Gabriela Kalna

  • 1Beatson Institute for Cancer Research, Glasgow, G61 1BD, UK.

Journal of Cell Science
|February 14, 2012
PubMed

Insights

Extracellular signal-regulated kinase 2 (ERK2) is crucial for cancer cell invasion, not redundant with ERK1. Suppressing ERK2 impairs cell motility by regulating Rab17 and liprin-β2 gene expression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The extracellular signal-regulated kinase (ERK) pathway is implicated in tumor invasion and progression.
  • ERK1 and ERK2 isoforms were considered redundant due to high homology and similar in vitro kinase activity.

Purpose of the Study:

  • To investigate the specific roles of ERK1 and ERK2 in cancer cell invasion.
  • To challenge the notion of functional redundancy between ERK1 and ERK2.

Main Methods:

  • Silencing of ERK2 in MDA-MB-231 cells.
  • Re-expression of ERK1 or ERK2 following knockdown.
  • Quantitative analysis of cell migration on 3D matrices.
  • Gene expression profiling using arrays.

Main Results:

  • ERK2 silencing inhibited invasive migration of MDA-MB-231 cells, while ERK1 did not.
  • ERK2 knockdown decreased cell migration velocity and increased non-motile time.
  • Expression of Rab17 and liprin-β2 genes, which inhibit invasion, was upregulated by ERK2 knockdown.
  • Re-expression of ERK2, but not ERK1, restored normal invasiveness and gene expression levels.
  • Knockdown of Rab17 or liprin-β2 rescued invasiveness in ERK2-depleted cells.

Conclusions:

  • ERK2 plays a non-redundant, critical role in driving cancer cell invasion.
  • ERK2 promotes invasion by suppressing the expression of inhibitory genes Rab17 and liprin-β2.
  • These findings highlight ERK2 as a potential therapeutic target for inhibiting cancer metastasis.

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