A high-content cellular senescence screen identifies candidate tumor suppressors, including EPHA3.

ABSTRACT: Activation of a cellular senescence program is a common response to prolonged oncogene activation or tumor suppressor loss, providing a physiological mechanism for tumor suppression in premalignant cells. The link between senescence and tumor suppression supports the hypothesis that a loss-of-function screen measuring bona fide senescence marker activation should identify candidate tumor suppressors. Using a high-content siRNA screening assay for cell morphology and proliferation measures, we identify 12 senescence-regulating kinases and determine their senescence marker signatures, including elevation of senescence-associated β-galactosidase, DNA damage and p53 or p16 (INK4a) expression. Consistent with our hypothesis, SNP array CGH data supports loss of gene copy number of five senescen

SUBMITTER: Lahtela J 

PROVIDER: S-EPMC3594263 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature