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Molecular Cancer
Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Short communication

Erk2 but not Erk1 regulates crosstalk between Met and EGFR in squamous cell carcinoma cell lines

Authors: Simone Gusenbauer, Emanuele Zanucco, Pjotr Knyazev, Axel Ullrich

Published in: Molecular Cancer | Issue 1/2015

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Abstract

Background

Squamous cell carcinoma (SCC) is the most common type of tongue and larynx cancer and a common type of lung cancer. In this study, we attempted to specifically evaluate the signaling pathway underlying HGF/Met induced EGFR ligand release in SSCs. The Met proto-oncogene encodes for a tyrosine kinase receptor which is often hyperactivated in human cancers. Met activation correlates with poor patient outcome. Several studies revealed a role of Met in receptor-crosstalk inducing either activation of other receptors, or inducing their resistance to targeted cancer treatments. In an epithelial tumor cell line screen we recently showed that the Met ligand HGF blocks the EGFR tyrosine kinase and at the same time activates transcriptional upregulation and accumulation in the supernatant of the EGFR ligand amphiregulin (Oncogene 32:3846–56, 2013). In the present work we describe the pathway responsible for the amphiregulin induction.

Findings

Amphiregulin is transcriptionally upregulated and is released into the supernatant. We show that Erk2 but not Erk1 mediates amphiregulin upregulation upon treatment with monocyte derived HGF. A siRNA knockdown of Erk2 completely abolishes amphiregulin release in squamous cell carcinomas.

Conclusions

These results identify Erk2 as the key downstream signal transducer between Met activation and EGFR ligand upregulation in squamous cell carcinoma cell lines derived from tongue, larynx and lung.
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Metadata
Title
Erk2 but not Erk1 regulates crosstalk between Met and EGFR in squamous cell carcinoma cell lines
Authors
Simone Gusenbauer
Emanuele Zanucco
Pjotr Knyazev
Axel Ullrich
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0319-z

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