Derepression of <i>hTERT</i> gene expression promotes escape from oncogene-induced cellular senescence

Abstract

Significance Normal cells respond to oncogenic signals by activating cellular senescence, a state of irreversible/permanent growth arrest that prevents cells from undergoing further cell divisions. Although this oncogene-induced senescence (OIS) is considered a critical tumor-suppressive mechanism, the irreversible nature of OIS remains controversial. In this study, we demonstrate that OIS is not always stable. After a prolonged period in senescence, cells can re-enter the cell-division cycle with epigenetic changes that facilitate cell transformation. Escape from OIS was promoted by derepression of hTERT gene expression, an enzyme that provides cellular immortality and is activated in &gt;90% of human cancers.