Journal article
Proteolytic enzymes and altered glycosylation modulate dystroglycan function in carcinoma cells
Cancer research (Chicago, Ill.), Vol.64(17), pp.6152-6159
2004
DOI: 10.1158/0008-5472.CAN-04-1638
PMID: 15342399
Abstract
Alterations in the basement membrane receptor dystroglycan (DG) are evident in muscular dystrophies and carcinoma cells and characterized by a selective loss or modification of the extracellular alpha-DG subunit. Defects in posttranslational modifications of DG have been identified in some muscular dystrophies, but the underlying modifications in carcinoma cells have not yet been defined. We reveal here multiple posttranslational modifications that modulate the composition and function of DG in normal epithelial cells and carcinoma cells. We show that alpha-DG is shed from the cell surface of normal and tumorigenic epithelial cells through a proteolytic mechanism that does not require direct cleavage of either alpha- or beta-DG. Shedding is dependent on metalloprotease activity and the proprotein convertase furin. Surprisingly, furin is also found to directly process alpha-DG as a proprotein substrate, changing the existing model of DG composition. We also show that the glycosylation of alpha-DG is altered in invasive carcinoma cells, and this modification causes complete loss of laminin binding properties. Together, these data elucidate several novel events regulating the functional composition of DG and reveal defects that arise during cancer progression, providing direction for efforts to restore this link with the basement membrane in carcinoma cells.
Details
- Title: Subtitle
- Proteolytic enzymes and altered glycosylation modulate dystroglycan function in carcinoma cells
- Creators
- Jarnail SINGH - California Pacific Medical Center Research Institute, San Francisco, California, United StatesYoko ITAHANA - California Pacific Medical Center Research Institute, San Francisco, California, United StatesSelena KNIGHT-KRAJEWSKI - California Pacific Medical Center Research Institute, San Francisco, California, United StatesMotoi KANAGAWA - Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa, United StatesKevin P CAMPBELL - Department of Physiology and Biophysics, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa, United StatesMina J BISSELL - Division of Life Sciences, Lawrence Berkeley National Laboratory, Berkeley, California, United StatesJohn MUSCHLER - California Pacific Medical Center Research Institute, San Francisco, California, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.64(17), pp.6152-6159
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- DOI
- 10.1158/0008-5472.CAN-04-1638
- PMID
- 15342399
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2004
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020633202771
Metrics
11 Record Views