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The cancer-associated meprin β variant G32R provides an additional activation site and promotes cancer cell invasion.

Henning SchäfflerWenjia LiOle HelmSandra KrügerChristine BögerFlorian PetersChristoph RöckenSusanne SebensRalph LuciusChristoph Becker-PaulyPhilipp Arnold
Published in: Journal of cell science (2019)
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-type meprin β. 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 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.
Keyphrases
  • cell surface
  • cell proliferation
  • amino acid
  • papillary thyroid
  • wild type
  • nitric oxide
  • squamous cell
  • squamous cell carcinoma
  • pi k akt
  • high resolution
  • mouse model
  • endoplasmic reticulum