The enemy within: An epigenetic role of retrotransposons in cancer initiation

Abstract

This article proposes that cancers can be initiated by retrotransposon (RTN) activation through changes in the transcriptional regulation of nearby genes. I first detail the hypothesis and then discuss the nature of physiological stress(es) in RTN activation; the role of DNA demethylation in the initiation and propagation of new RTN states; the connection between ageing and cancer incidence and the involvement of activated RTNs in the chromosomal aberrations that feature in cancer progression. The hypothesis neither replaces nor invalidates other theories of cancer, in particular the somatic mutation theory, but helps clarify and unify much of the hitherto poorly integrated, complex phenomenology of cancer.

The intron-enriched HERV-K(HML-10) family suppresses apoptosis, an indicator of malignant transformation

“…However, the presence of HML-10(DAP3) RNA in many tumor cell lines and the absence in most healthy tissues (Table 2) suggest that its upregulation may be a relevant feature in some human cancer diseases. This is in line with the observation that transcriptional activation of HERVs and other REs by epigenetic DNA demethylation is a frequent characteristic of malignant cells [64–66]. …”

RAE1 Ligands for the NKG2D Receptor Are Regulated by STING-Dependent DNA Sensor Pathways in Lymphoma

“…An intriguing question is where cytosolic DNA originates from and the mechanism leading to cytosolic DNA in tumor cells. DNA damage is known to induce transcription of retroelements, including transposases, derived from functional endogenous retrovirus present in the genome (41). Alternatively, cytosolic DNA could be generated during DDR-dependent DNA-repair that can result in deletion of genomic DNA.…”

A Brief History of the Status of Transposable Elements: From Junk DNA to Major Players in Evolution

“…Some sequences will be found to play major roles while others will undoubtedly be found to be only selfish. Such research is likely to have a major impact in the field of cancer, some of the phenomenology of which involves both epigenetic processes and TE reactivation (Serafino et al 2009;Lamprecht et al 2010;Shalgi et al 2010;Wilkins 2010). TEs and all the other repeated sequences might, once again, have some major new surprises in store for us.…”