Figure 3.

HERV‐K related oncogenesis. (A) LTRs through their promoter and enhancer functions modulate the expression of host genes and thus participate in human carcinogenesis. (B) HERV‐K protein expression appears to exert oncogenic functions including the induction of the hallmarks of cancer and increased cellular oxidative stress, the activation of cancer‐related molecular pathways like the ERK, AKT, and Notch pathway, and the upregulation of β‐catenin. Furthermore, Np9 and Rec seem to bind to ZFPs (PLZF and TZFP) and prevent them from repressing the c‐myc proto‐oncogene expression. Finally, HERV‐K specific immunogenicity has been correlated to multiple malignancies. (C) Presence of HERV‐K noninfectious virions and viral‐like particles have been correlated to human malignancy, most strikingly in the case of teratocarcinoma. (D) Transactivation of HERVs induced by known onco‐virus and intra‐viral interactions between HERV‐K and onco‐viruses have also been linked to the development of the hallmarks of cancer in multiple virally mediated cancers.

ERK, extracellular‐signal regulated kinase; HERV, human endogenous retrovirus; LTR, long terminal repeat; PLZF, promyelocytic leukemia zinc finger; TZFP, testicular zinc finger protein; ZFP, zinc finger protein. Created with BioRender.com.