| Autor: |
Pelletier L; Génétique moléculaire, Signalisation et Cancer, UMR 5201, Faculté de Médecine, 8 Avenue Rockefeller, 69-373 Lyon Cedex 08, France., Guillaumot P, Frêche B, Luquain C, Christiansen D, Brugière S, Garin J, Manié SN |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer research [Cancer Res] 2006 Apr 01; Vol. 66 (7), pp. 3681-7. |
| DOI: |
10.1158/0008-5472.CAN-05-3870 |
| Abstrakt: |
The metalloprotease-dependent extracellular domain cleavage of the adhesion molecule CD44 is frequently observed in human tumors and is thought to promote metastasis. This cleavage is followed by gamma-secretase-dependent release of CD44 intracellular domain (CD44-ICD), which exhibits nuclear signaling activity. Using a reversible Ret-dependent oncogenic conversion model and a restricted proteomic approach, we identified a positive correlation between the neoplastic transformation of Rat-1 cells and the expression of standard CD44. In these transformed cells, CD44 was found to undergo a sequential metalloprotease and gamma-secretase cleavage, resulting in an increase in expression of CD44-ICD. We showed that this proteolytic fragment possesses a transforming activity. In support of this role, a significant and specific reduction in Ret-induced transformation of Rat-1 cells was observed following drug-mediated inhibition of gamma-secretase. Taken together, these findings suggest that the shedding of CD44 may not only modulate metastasis but also affects earlier events in tumorigenesis through the release of CD44-ICD. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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