Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer

Authors: Atma Ivancevic, David M. Simpson, Olivia M. Joyner, Stacey M. Bagby, Lily L. Nguyen, Ben G. Bitler, Todd M. Pitts, Edward B. Chuong

Published: 2024-07-17

DOI: 10.1126/sciadv.ado1218

Source: Full article


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 MAPK/AP1 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