Research Papers:

Intravesicular epidermal growth factor receptor subject to retrograde trafficking drives epidermal growth factor-dependent migration

Sabrina Maisel, Derrick Broka and Joyce Schroeder _

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Oncotarget. 2018; 9:6463-6477. https://doi.org/10.18632/oncotarget.23766

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Sabrina Maisel1,2, Derrick Broka2 and Joyce Schroeder1,2,3,4

1Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA

2Arizona Cancer Center, University of Arizona, Tucson, AZ, USA

3Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA

4BIO5 Institute, University of Arizona, Tucson, AZ, USA

Correspondence to:

Joyce Schroeder, email: [email protected]

Keywords: epidermal growth factor receptor; MUC1; cetuximab; migration; retrograde trafficking

Received: September 21, 2017     Accepted: December 23, 2017     Published: December 29, 2017


The Epidermal Growth Factor Receptor (EGFR) is frequently mutated and overexpressed in metastatic cancer. Although EGFR is a transmembrane tyrosine kinase localized to the basolateral membrane in normal epithelium, it is frequently found intracellularly localized in transformed cells. We have previously demonstrated the epithelial adaptor protein mucin 1 (MUC1) alters trafficking of EGFR, inhibiting its degradation and promoting its translocation to the nucleus, where it can directly modulate gene transcription. Here, we demonstrate that MUC1 promotes the retention of EGF-bound EGFR in Early Endosome Antigen1 (EEA1)-positive vesicles while preventing its trafficking to the lysosome. These events result in the accumulation of endosomal vesicles harboring active receptor throughout the cell and a reorganization of the actin cytoskeleton. EGF-dependent cell migration and filopodia formation is reliant upon this altered trafficking, and can be prevented by blocking retrograde trafficking. Together, these results indicate that intracellular EGFR may play an essential role in cancer metastasis and a potential mechanism for the failure of therapeutic antibodies in EGFR-driven metastatic breast cancer.

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