| Autor: |
Lorenzato, Annalisa, Martino, Cosimo, Dani, Nadia, Oligschläger, Yvonne, Ferrero, Anna Maria, Biglia, Nicoletta, Calogero, Raffaele, Olivero, Martina, Di Renzo, Maria Flavia |
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| Zdroj: |
FASEB Journal; Jun2012, Vol. 26 Issue 6, p2446-2456, 11p |
| Abstrakt: |
The cellular apoptosis susceptibility gene CAS/CSE1L is overexpressed in cancer, although it was originally identified as a gene that renders cells vulnerable to apoptotic stimuli. CAS/CSE1L has roles in the nucleocyto-plasmic recycling of importin-αand in the regulation of gene expression, cell migration, and secretion. We identified CAS/CSE1L as a survival factor for ovarian cancer cells in vitro and in vivo. In 3/3 ovarian cancer cell lines, CAS/ CSE1L was down-modulated by the unorthodox proapoptotic signaling of the MET receptor. CAS/CSE1L knockdown with RNA interference committed the ovarian cancer cells to death, but not immortalized normal cells and breast and colon cancer cells. In 70 and 95% of these latter cells, respectively, CAS/CSE1L was localized in the cytoplasm, while it accumulated in the nucleus in >90% of ovarian cancer cells. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells. In the nucleus, CAS/CSE1L regulated the expression of the proapoptotic Ras-association domain family 1 gene products RASSF1C and RASSF1A, which mediated death signals evoked by depletion of CAS/CSE1L. Our data show that CAS/CSE1L protects ovarian cancer cells from death through transcriptional suppression of a proapoptotic gene and suggest that the localization of CAS/CSE1L dictates its function. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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