Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer. Journal Article uri icon

Overview

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 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.

publication date

  • July 19, 2024

has subject area

has restriction

  • gold

Date in CU Experts

  • July 24, 2024 4:11 AM

Full Author List

  • Ivancevic A; Simpson DM; Joyner OM; Bagby SM; Nguyen LL; Bitler BG; Pitts TM; Chuong EB

author count

  • 8

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Additional Document Info

start page

  • eado1218

volume

  • 10

issue

  • 29