Project Overview: The phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the most frequently mutated genes in human cancers (15% of tumour samples tested, COSMIC database, Sanger Institute). Functionally, PTEN is a tumour suppressor that negatively regulates the PI3K/AKT signaling cascade, thereby buffering its pro-survival, pro-proliferative and anti-apoptotic signals.The use of isogenic cell lines differing only in the presence/absence of a single gene, in combination with synthetic lethal siRNA screening technology, provide us with a powerful and unbiased way to identify dependencies that solely occur upon a specific lesion. The proposed project is going to employ such a synthetic lethal siRNA screen in a PTEN-isogenic cell system, in pursuit of dependencies occurring upon loss of the tumour suppressor gene PTEN. Hits revealed by this screen will be tested for their ability to generally impair the viability of PTEN-null genotypes using a panel of human PTEN-expressing and PTEN-null cancer cell lines, and their functional characterization will be pursued.If successful, the proposed project may lead to the discovery of novel potential therapeutic targets against PTEN-non-expressing tumours. 
Screener: George Vlachogiannis (Downward Lab).
Extension:3365, Rm 206
Project Status: Validating Hits
Project Start Date: Dec 2010
Keywords: PTEN
Viability
Libraries Screened:
  •   Combined Kinase, GPCR, Druggable
  •   Full Genome 96
  •   Custom Order - George
  •   Cherry Pick - George