ERK2 but not ERK1 mediates HGF-induced motility in non-small cell lung carcinoma cell lines

Simone Radtke, Mina Milanovic, Carine Rossé, Manu De Rycker, Sylvie Lachmann, Andrew Hibbert, Stéphanie Kermorgant, Peter J. Parker

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


Aberrant signalling of receptor tyrosine kinases (RTKs), such as c-Met, the receptor for hepatocyte growth factor (HGF), has been implicated in the oncogenesis of various tumours including non-small cell lung carcinoma (NSCLC). Through its pro-migratory properties, c-Met has been implicated specifically in the process of tumour metastasis, demandinga better understanding of the underlying signalling pathways. Various players downstream of c-Met have been well characterised, including the extracellular-signalregulated kinases (ERKs) 1 and 2. In a small interfering RNA (siRNA)-based high-throughput wound healing screen performed in A549 lung carcinoma cells, we identified ERK2 but not ERK1 as a strong mediator of HGF-induced motility. This finding was confirmed in several NSCLC cell lines as well as in HeLa cells. One known substrate for ERK kinases in cell migration, the focal adhesion protein paxillin, was also one of the hits identified in the screen. We demonstrate that HGF stimulation results in a time-dependent phosphorylation of paxillin on serine 126, a process that can be blocked by inhibition of the ERK1/2 upstream kinase mitogen-activated protein kinase/ERK kinase 1 (MEK1) or inhibition of glycogen synthase kinase 3 (GSK3). Further, we show that paxillin turnover at focal adhesions is increased upon stimulation by HGF, an effect that is dependent on serine residues 126 (GSK3 site) and 130 (ERK site) within paxillin. In line with the isoform-specific requirement of ERK2 for HGF-mediated migration in lung tumour cell models, ERK2 but not ERK1 is shown to be responsible for paxillin serine 126 phosphorylation and its increased turnover at focal adhesions.

Original languageEnglish
Pages (from-to)2381-2391
Number of pages11
JournalJournal of Cell Science
Issue number11
Publication statusPublished - 12 Jun 2013


  • c-Met
  • ERK2
  • HGF
  • High-throughput screen
  • Motility
  • Paxillin
  • Signalling
  • siRNA
  • Wound healing

ASJC Scopus subject areas

  • Cell Biology


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