Back to Search
Start Over
AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells
- Source :
- Experimental cell research. 319(17)
- Publication Year :
- 2013
-
Abstract
- The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals.
- Subjects :
- Transcriptional Activation
Cytoplasm
Nucleocytoplasmic Transport Proteins
Transcription, Genetic
Active Transport, Cell Nucleus
Biology
Metastasis
Cell Movement
Cellular Apoptosis Susceptibility Protein
Cell Line, Tumor
Gene expression
medicine
Gene silencing
Humans
Phosphorylation
Protein kinase B
Transcription factor
Cell Nucleus
Ovarian Neoplasms
Gene Expression Profiling
Nuclear Proteins
Cell Biology
medicine.disease
Cell biology
Gene Expression Regulation, Neoplastic
Cancer cell
Cancer research
Female
Nuclear transport
Ovarian cancer
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 10902422
- Volume :
- 319
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....d0faca56aae99faed3fcca14981d20b3