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

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Gusenbauer,  Simone
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Zanucco,  Emanuele
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Knyazev,  Pjotr
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Ullrich,  Axel
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

Gusenbauer, S., Zanucco, E., Knyazev, P., & Ullrich, A. (2015). Erk2 but not Erk1 regulates crosstalk between Met and EGFR in squamous cell carcinoma cell lines. MOLECULAR CANCER, 14: 54. doi:10.1186/s12943-015-0319-z.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-002A-4147-8
Zusammenfassung
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.