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The cancer-associated meprin β variant G32R provides an additional activation site and promotes cancer cell invasion.
- Source :
-
Journal of Cell Science . Jun2019, p1-9. 9p. - Publication Year :
- 2019
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Abstract
- The extracellular metalloprotease meprin β is expressed as a homodimer and is primarily membrane bound. Meprin β can be released from the cell surface by its known sheddases ADAM10 and ADAM17. Activation of pro-meprin β at the cell surface prevents its shedding, thereby stabilizing its proteolytic activity at the plasma membrane. We show that a single amino acid exchange variant (G32R) of meprin β, identified in endometrium cancer, is more active against a peptide substrate and the IL-6 receptor than wild-typemeprin β.We demonstrate that the change to an arginine residue at position 32 represents an additional activation site used by furin-like proteases in theGolgi,which consequently leads to reduced shedding by ADAM17. We investigated this meprin β G32R variant to assess cell proliferation, invasion through a collagen IV matrix and outgrowth from tumor spheroids. We found that increased meprin β G32R activity at the cell surface reduces cell proliferation, but increases cell invasion. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219533
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 136792856
- Full Text :
- https://doi.org/10.1242/jcs.220665