| First Author | Schäffler H | Year | 2019 |
| Journal | J Cell Sci | Volume | 132 |
| Issue | 11 | PubMed ID | 31076514 |
| Mgi Jnum | J:277779 | Mgi Id | MGI:6317068 |
| Doi | 10.1242/jcs.220665 | Citation | Schaffler H, et al. (2019) The cancer-associated meprin beta variant G32R provides an additional activation site and promotes cancer cell invasion. J Cell Sci 132(11):jcs220665 |
| abstractText | The extracellular metalloprotease meprin beta is expressed as a homodimer and is primarily membrane bound. Meprin beta can be released from the cell surface by its known sheddases ADAM10 and ADAM17. Activation of pro-meprin beta 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 beta, identified in endometrium cancer, is more active against a peptide substrate and the IL-6 receptor than wild-type meprin beta. We demonstrate that the change to an arginine residue at position 32 represents an additional activation site used by furin-like proteases in the Golgi, which consequently leads to reduced shedding by ADAM17. We investigated this meprin beta G32R variant to assess cell proliferation, invasion through a collagen IV matrix and outgrowth from tumor spheroids. We found that increased meprin beta G32R activity at the cell surface reduces cell proliferation, but increases cell invasion. |
