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

Aberrant mucin type O-linked glycosylation is a common occurrence in cancer. This type of O-linked glycosylation can occur on many cell surface glycoproteins where only a small number of sites may be present. EGFR is one such glycoprotein. 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, breast cancer cells carrying different O-linked glycans respond by transcribing differential 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 appears to be regulated by the formation of a EGFR/galectin-3/MUC1 complex at the cell surface that is present in cells carrying short core1-based O-glycans characteristic of tumour cells but absent in core 2 O-glycan carrying cells representative of normal mammary epithelial cells. Overall design: T47D non-treated control cells, T47D cells treated with EGF for 2h, T47D cells treated with EGF for 6h, E2J non-treated control cells, E2J cells treated with EGF for 2h, E2J cells treated with EGF for 6h.3 biological replicates for each condition were used. Technical duplicates were run of T47D non reated control samples and T47D cells treated with EGF for 2h.