Application of RNA-Seq transcriptome analysis: CD151 is an Invasion/Migration target in all stages of epithelial ovarian cancer

Rebecca A. Mosig, Li Lin, Emir Senturk, Hardik Shah, Fei Huang, Peter Schlosshauer, Samantha Cohen, Robert Fruscio, Sergio Marchini, Maurizio D'Incalci, Ravi Sachidanandam, Peter Dottino, John A. Martignetti

Research output: Contribution to journalArticlepeer-review

Abstract

Background: RNA-Seq allows a theoretically unbiased analysis of both genome-wide transcription levels and mutation status of a tumor. Using this technique we sought to identify novel candidate therapeutic targets expressed in epithelial ovarian cancer (EOC). Methods. Specifically, we sought candidate invasion/migration targets based on expression levels across all tumors, novelty of expression in EOC, and known function. RNA-Seq analysis revealed the high expression of CD151, a transmembrane protein, across all stages of EOC. Expression was confirmed at both the mRNA and protein levels using RT-PCR and immunohistochemical staining, respectively. Results: In both EOC tumors and normal ovarian surface epithelial cells we demonstrated CD151 to be localized to the membrane and cell-cell junctions in patient-derived and established EOC cell lines. We next evaluated its role in EOC dissemination using two ovarian cancer-derived cell lines with differential levels of CD151 expression. Targeted antibody-mediated and siRNA inhibition or loss of CD151 in SKOV3 and OVCAR5 cell lines effectively inhibited their migration and invasion. Conclusion: Taken together, these findings provide the first proof-of-principle demonstration for a next generation sequencing approach to identifying candidate therapeutic targets and reveal CD151 to play a role in EOC dissemination.

Original languageEnglish
Article number4
JournalJournal of Ovarian Research
Volume5
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • CD151
  • Epithelial Ovarian Cancer
  • Invasion
  • Metastasis
  • Migration
  • RNA-Seq

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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