Transposable Element Activation: A Hallmark of Cancer

Transposable elements (TEs), mobile DNA sequences that can move independently about the genome, make up about half of the human genome and are mostly silenced by epigenetic modifications in healthy differentiated cells. Global epigenetic dysregulation during oncogenic transformation causes TE expression, contributing to transcriptional rewiring and TE activity as insertional mutagens. TE nucleic acids are sensed in the cytoplasm, initiating inflammation that can be therapeutically manipulated to activate anti-tumor immune responses. Here we detail how TEs contribute to six of the classic hallmarks of cancer and propose widespread TE expression and activation as a new hallmark of cancer.