Interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in human epithelial cancer cells

Piyush, T, Chacko, AR, Sindrewicz, P, Hilkens, J, Rhodes, JM ORCID: 0000-0002-1302-260X and Yu, LG ORCID: 0000-0001-9641-3712 (2017) Interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in human epithelial cancer cells. Cell Death and Differentiation, 24 (11). pp. 1937-1947.

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Official URL: https://www.nature.com/articles/cdd2017119

Abstract

Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell growth and survival in normal and cancerous tissues and is a principal therapeutic target for cancer treatment. EGFR is associated in epithelial cells with the heavily glycosylated transmembrane mucin protein MUC1, a natural ligand of galectin-3 that is overexpressed in cancer. This study reveals that the expression of cell surface MUC1 is a critical enhancer of EGF-induced EGFR activation in human breast and colon cancer cells. Both the MUC1 extracellular and intracellular domains are involved in EGFR activation but the predominant influence comes from its extracellular domain. Binding of galectin-3 to the MUC1 extracellular domain induces MUC1 cell surface polarization and increases MUC1–EGFR association. This leads to a rapid increase of EGFR homo-/hetero-dimerization and subsequently increased, and also prolonged, EGFR activation and signalling. This effect requires both the galectin-3 C-terminal carbohydrate recognition domain and its N-terminal ligand multi-merization domain. Thus, interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in epithelial cancer cells. As MUC1 and galectin-3 are both commonly overexpressed in most types of epithelial cancers, their interaction and impact on EGFR activation likely makes important contribution to EGFR-associated tumorigenesis and cancer progression and may also influence the effectiveness of EGFR-targeted cancer therapy.

Item Type:	Article
Uncontrolled Keywords:	glycobiology, oncogenes
Depositing User:	Symplectic Admin
Date Deposited:	04 Jul 2017 09:00
Last Modified:	19 Jan 2023 07:00
DOI:	10.1038/cdd.2017.119
Open Access URL:	http://dx.doi.org/10.1038/cdd.2017.119
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008309