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Subcellular localization of EGFR in esophageal carcinoma cell lines

  • RESEARCH ARTICLE
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

Background: The EGF receptor is a therapeutic target in cancer cells, whereby mutations of EGFR and/or signalling members act as predictive markers. EGFR however also exhibits dynamic changes of subcellular localization, leading to STAT5 complex formation, nuclear translocation and induction of Aurora-A expression in squamous cancer cells. We previously described high EGFR and Aurora-A expression in esophageal cancer cells. Here, we investigated subcellular localization of EGFR and STAT5 in esophageal cancer cells. Results: Quantitative immunofluorescence analyses of four esophageal cancer cell lines reflecting esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) revealed that the subcellular localization of EGFR was shifted from a membranous to cytoplasmic localization upon EGF-stimulation in OE21 (ESCC) cells. Thereby, EGFR in part co-localized with E-Cadherin. In parallel, phosphorylated STAT5-Tyr694 appeared to increase in the nucleus and to decrease at the cell membrane. In three additional cell lines, EGFR was only marginally (Kyse-410/ESCC; OE19/EAC) and weakly (OE33, EAC) detectable at the cell membrane. Partial co-localization of EGFR and E-Cadherin occurred in OE33 cells. Post EGF-stimulation, EGFR was detected in the cytoplasm, resembling endosomal compartments. Furthermore, OE19 and OE33 exhibited nuclear STAT5-Tyr694 phosphorylation upon EGF-stimulation. None of the four cell lines showed nuclear EGFR expression and localization. Conclusion: In contrast to other (squamous) cancer cells, activation of EGFR in esophageal squamous cancer cells does not result in nuclear translocation of EGFR. Still, the subcellular localization of EGFR may influence STAT5-associated signaling pathways in esophageal cancer cells and hence possibly also the responses to ErbB, respective EGFR-targeted therapies.

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Abbreviations

EAC:

Esophageal Adenocarcinoma

EGF:

Epidermal Growth Factor

EGFR:

Epidermal Growth Factor Receptor

ESCC:

Esophageal Squamous Cell Carcinoma

PBS:

Phosphate buffered saline

STAT:

Signal Transducer and Activator of Transcription

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Acknowledgments

The authors acknowledge technical support of Ms. Anja Schoepflin and Ms. Nicola Bittermann as well as proofreading of the manuscript by K. Schneider. The study was supported by the Deutsche Forschungsgemeinschaft (SFB850 grant C5 to SL, MW) and in part by the Mushett Family Foundation (Chester, NJ, USA; grant to SL, MW).

Authors contributions

LS, CF: Performed and analyzed experiments, wrote manuscript; MW: contributed morpho−/cytological interpretation, discussed results, approved manuscript, provided resources; SL: Designed study, analyzed data, wrote manuscript, provided resources.

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Authors and Affiliations

  1. Institute of Surgical Pathology, Department of Pathology, University Medical Center, Breisacherstrasse 115A, 79106, Freiburg, Germany

    Lucas Spohn, Christiane Fichter, Martin Werner & Silke Lassmann

  2. German Consortium for Translational Cancer Research (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Martin Werner & Silke Lassmann

  3. BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany

    Silke Lassmann

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  1. Lucas Spohn
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  2. Christiane Fichter
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  3. Martin Werner
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  4. Silke Lassmann
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Correspondence to Silke Lassmann.

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Spohn, L., Fichter, C., Werner, M. et al. Subcellular localization of EGFR in esophageal carcinoma cell lines. J. Cell Commun. Signal. 10, 41–47 (2016). https://doi.org/10.1007/s12079-015-0308-4

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  • DOI: https://doi.org/10.1007/s12079-015-0308-4

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