Journal article
Loss of α-Dystroglycan Laminin Binding in Epithelium-derived Cancers Is Caused by Silencing of LARGE
The Journal of biological chemistry, Vol.284(17), pp.11279-11284
04/24/2009
DOI: 10.1074/jbc.C900007200
PMCID: PMC2670132
PMID: 19244252
Abstract
The interaction between epithelial cells and the extracellular matrix is crucial for tissue architecture and function and is compromised during cancer progression. Dystroglycan is a membrane receptor that mediates interactions between cells and basement membranes in various epithelia. In many epithelium-derived cancers, β-dystroglycan is expressed, but α-dystroglycan is not detected. Here we report that α-dystroglycan is correctly expressed and trafficked to the cell membrane but lacks laminin binding as a result of the silencing of the like-acetylglucosaminyltransferase (LARGE) gene in a cohort of highly metastatic epithelial cell lines derived from breast, cervical, and lung cancers. Exogenous expression of LARGE in these cancer cells restores the normal glycosylation and laminin binding of α-dystroglycan, leading to enhanced cell adhesion and reduced cell migration in vitro. Our findings demonstrate that LARGE repression is responsible for the defects in dystroglycan-mediated cell adhesion that are observed in epithelium-derived cancer cells and point to a defect of dystroglycan glycosylation as a factor in cancer progression.
Details
- Title: Subtitle
- Loss of α-Dystroglycan Laminin Binding in Epithelium-derived Cancers Is Caused by Silencing of LARGE
- Creators
- Daniel Beltrán-Valero de Bernabé - Howard Hughes Medical Institute, Iowa City, Iowa 52242-1101Kei-ichiro Inamori - Howard Hughes Medical Institute, Iowa City, Iowa 52242-1101Takako Yoshida-Moriguchi - Howard Hughes Medical Institute, Iowa City, Iowa 52242-1101Christine J Weydert - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242-1101Hollie A Harper - Howard Hughes Medical Institute, Iowa City, Iowa 52242-1101Tobias Willer - Howard Hughes Medical Institute, Iowa City, Iowa 52242-1101Michael D Henry - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242-1101Kevin P Campbell - Howard Hughes Medical Institute, Iowa City, Iowa 52242-1101
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.284(17), pp.11279-11284
- DOI
- 10.1074/jbc.C900007200
- PMID
- 19244252
- PMCID
- PMC2670132
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Grant note
- RO1 CA130916 / National Institutes of Health
- Alternative title
- Loss of alpha-dystroglycan laminin binding in epithelium-derived cancers is caused by silencing of LARGE
- Language
- English
- Date published
- 04/24/2009
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Urology; Internal Medicine
- Record Identifier
- 9984068263602771
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