TMEFF2 shedding is regulated by oxidative stress and mediated by ADAMs and transmembrane serine proteases implicated in prostate cancer.
Cell Biol Int
; 42(3): 273-280, 2018 Mar.
Article
en En
| MEDLINE
| ID: mdl-28762604
TMEFF2 is a type I transmembrane protein with two follistatin (FS) and one EGF-like domain over-expressed in prostate cancer; however its biological role in prostate cancer development and progression remains unclear, which may, at least in part, be explained by its proteolytic processing. The extracellular part of TMEFF2 (TMEFF2-ECD) is cleaved by ADAM17 and the membrane-retained fragment is further processed by the gamma-secretase complex. TMEFF2 shedding is increased with cell crowding, a condition associated with the tumour microenvironment, which was mediated by oxidative stress signalling, requiring jun-kinase (JNK) activation. Moreover, we have identified that TMEFF2 is also a novel substrate for other proteases implicated in prostate cancer, including two ADAMs (ADAM9 and ADAM12) and the type II transmembrane serine proteinases (TTSPs) matriptase-1 and hepsin. Whereas cleavage by ADAM9 and ADAM12 generates previously identified TMEFF2-ECD, proteolytic processing by matriptase-1 and hepsin produced TMEFF2 fragments, composed of TMEFF2-ECD or FS and/or EGF-like domains as well as novel membrane retained fragments. Differential TMEFF2 processing from a single transmembrane protein may be a general mechanism to modulate transmembrane protein levels and domains, dependent on the repertoire of ADAMs or TTSPs expressed by the target cell.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Estrés Oxidativo
/
Proteínas ADAM
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Proteínas de la Membrana
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Cell Biol Int
Año:
2018
Tipo del documento:
Article
País de afiliación:
Polonia
Pais de publicación:
Reino Unido