title: MUC1 extracellular domain confers resistance of epithelial cancer cells to anoikis.
abstract: Anoikis, a special apoptotic process occurring in response to loss of cell adhesion to the extracellular matrix, is a fundamental surveillance process for maintaining tissue homeostasis. Resistance to anoikis characterises cancer cells and is a pre-requisite for metastasis. This study shows that overexpression of the transmembrane mucin protein MUC1 prevents initiation of anoikis in epithelial cancer cells in response to loss of adhesion. We show that this effect is largely attributed to the elongated and heavily glycosylated extracellular domain of MUC1 that protrudes high above the cell membrane and hence prevents activation of the cell surface anoikis-initiating molecules such as integrins and death receptors by providing them a mechanically 'homing' microenvironment. As overexpression of MUC1 is a common feature of epithelial cancers and as resistance to anoikis is a hallmark of both oncogenic epithelial-mesenchymal transition and metastasis, MUC1-mediated cell resistance to anoikis may represent one of the fundamental regulatory mechanisms in tumourigenesis and metastasis.
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: T
authors.initials: T
authors.lastname: Piyush
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Centre, Omaha, NE, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Hollingsworth
authors.affiliation: Division of Molecular Genetics, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Hilkens
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Rhodes
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: L-G
authors.initials: LG
authors.lastname: Yu
mesh_terms: D023102:Anoikis; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D018396:Mucin-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017434:Protein Structure, Tertiary
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1