O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR in breast cancer

Author:

Tajadura-Ortega Virginia,Gambardella Gennaro,Skinner Alexandra,Schjoldager Katrine Ter-Borch Gram,Beatson Richard,Graham Rosalind,Achkova Daniela,Taylor-Papadimitriou Joyce,Ciccarelli Francesca D.,Burchell Joy M.ORCID

Abstract

ABSTRACTAberrant mucin type O-linked glycosylation is a common occurrence in cancer. This type of O-linked glycosylation is not limited to mucins but can occur on many cell surface glycoproteins where only a small number of sites may be present. Upon EGF ligation, EGFR induces a signaling cascade but can also translocate to the nucleus where it can directly regulate gene transcription. Here we show that upon EGF binding, human breast cancer cells carrying different O-linked glycans respond by transcribing different gene expression signatures. This is not a result of changes in signal transduction but due to the differential nuclear translocation of EGFR in the two glyco-phenotypes. This is regulated by the formation of an EGFR/galectin-3/MUC1/β-catenin complex at the cell surface that is present in cells carrying short core-1-based O-glycans characteristic of tumour cells but absent in core-2-carrying cells.

Publisher

Cold Spring Harbor Laboratory

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