AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells

Annalisa Lorenzato, Marta Biolatti, Giuseppe Delogu, Giampiero Capobianco, Cristiano Farace, Salvatore Dessole, Antonio Cossu, Francesco Tanda, Roberto Madeddu, Martina Olivero, Maria Flavia Di Renzo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2627-2636
Number of pages10
JournalExperimental Cell Research
Volume319
Issue number17
DOIs
Publication statusPublished - Oct 15 2013

Keywords

  • Chromosome segregation 1-like protein CSE1L
  • Expression profiling
  • Nuclear transport
  • Ovarian cancer

ASJC Scopus subject areas

  • Cell Biology

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