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• W2780075557 abstract "// Sabrina Maisel 1, 2 , Derrick Broka 2 and Joyce Schroeder 1, 2, 3, 4 1 Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA 2 Arizona Cancer Center, University of Arizona, Tucson, AZ, USA 3 Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA 4 BIO5 Institute, University of Arizona, Tucson, AZ, USA Correspondence to: Joyce Schroeder, email: joyces@email.arizona.edu Keywords: epidermal growth factor receptor; MUC1; cetuximab; migration; retrograde trafficking Received: September 21, 2017      Accepted: December 23, 2017      Published: December 29, 2017 ABSTRACT 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." @default.
• W2780075557 created "2018-01-05" @default.
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• W2780075557 date "2017-12-29" @default.
• W2780075557 modified "2023-10-01" @default.
• W2780075557 title "Intravesicular epidermal growth factor receptor subject to retrograde trafficking drives epidermal growth factor-dependent migration" @default.
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• W2780075557 doi "https://doi.org/10.18632/oncotarget.23766" @default.
• W2780075557 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5814225" @default.
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