Katherine Chiappinelli: How Jumping Genes Rewire Cancer Cells and Fuel Tumor Growth

Katherine Chiappinelli, Associate Professor of Microbiology, Immunology and Tropical Medicine at The George Washington University, shared on LinkedIn: ”When the human genome was sequenced in 2003, one of the most striking findings was that only 1-2% of the genome codes for proteins. The majority is made up of repetitive DNA and transposable elements (TEs). TEs are self-propagating pieces of DNA that can move about the genome and are active from plants to humans. TEs contribute to gene regulation and cellular processes in healthy and diseased tissues, but are notably dysregulated and overexpressed in cancers. In this review for Cancer Discovery (AACR Journals), Kathleen Burns and I summarize the existing literature on TEs in cancer: how they can transcriptionally rewire cancer cells, cause genome instability, and activate innate and adaptive anti-tumor immune responses. In the accompanying In Focus piece, Benjamin Greenbaum and Siyu Sun describe how self RNAs, including TE sequences, activate innate immune signaling (viral mimicry) in cancer. Overall, 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. Further, TE expression can be considered a therapeutic vulnerability in cancer, as TEs may cause
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