{"doi":"10.1101/2021.10.28.466196","title":"Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer","abstract":"Abstract Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the mechanisms underlying the formation of these pathological networks remain poorly understood. Through a pan-cancer epigenomic analysis, we found that primate-specific endogenous retroviruses (ERVs) are a rich source of enhancers displaying cancer-specific activity. In colorectal cancer and other epithelial tumors, oncogenic AP1/MAPK signaling drives the activation of enhancers derived from the primate-specific ERV family LTR10. Functional studies in colorectal cancer cells revealed that LTR10 elements regulate tumor-specific expression of multiple genes associated with tumorigenesis, such as ATG12 and XRCC4 . Within the human population, individual LTR10 elements exhibit germline and somatic structural variation resulting from a highly mutable internal tandem repeat region, which affects AP1 binding activity. Our findings reveal that ERV-derived enhancers contribute to transcriptional dysregulation in response to oncogenic signaling and shape the evolution of cancer-specific regulatory networks.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215615,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":810443,"name":"David Simpson","orcid":"0000-0001-9538-3208","position":1,"is_corresponding":false},{"id":810940,"name":"Olivia Joyner","orcid":null,"position":2,"is_corresponding":false},{"id":394520,"name":"Stacey M. Bagby","orcid":"0009-0005-3355-3861","position":3,"is_corresponding":false},{"id":810444,"name":"Lily L. Nguyen","orcid":"0000-0003-4425-2536","position":4,"is_corresponding":false},{"id":246398,"name":"Benjamin G. Bitler","orcid":"0000-0002-5809-5271","position":5,"is_corresponding":false},{"id":394519,"name":"Todd M. Pitts","orcid":"0000-0002-8123-9894","position":6,"is_corresponding":false},{"id":810445,"name":"Edward B. Chuong","orcid":"0000-0002-5392-937X","position":7,"is_corresponding":false},{"id":810442,"name":"Atma M. Ivancevic","orcid":"0000-0002-0101-9876","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-18T23:52:55.971300Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}