Table 2.
Main molecular evidence of putative pro-oncogenic activity of HERV-derived Env.
| Group | Env protein | Tumor type | Molecular mechanism | Oncogenic effect | References |
|---|---|---|---|---|---|
| HERV-W | Syncytin-1 (7q21.2) | Breast | Fusogenicity | Cell-cell fusion | Bjerregaard et al., 2006 |
| Endometrial | Fusogenicity | Cell-cell fusion | Strick et al., 2007; Strissel et al., 2012 | ||
| Neuroblastoma | Cellular pathway alteration | SK3 hyperactivation, excitotoxicity | Li et al., 2013 | ||
| Bladder urothelial cells | Unknown | Increased cell proliferation and viability | Yu et al., 2014 | ||
| HERV-FRD | Syncytin-2 (6p24.1) | Breast | Ectopic GMC1-induced fusogenicity | Cell-cell fusion | Liang et al., 2010 |
| Endometrial | Fusogenicity | Cell-cell fusion | Strissel et al., 2012 | ||
| HERV-K (HML2) | Env | Breast | Stimulation of cellular pathways playing key roles in cancer (EGFR, TGFB1, NF-κB, c-myc, p53, Ras, p-RSK, p-ERK1/2…) | Increased cell proliferation, transformation, migration and invasion | Zhou et al., 2016; Lemaître et al., 2017 |
| Rec | Germ cell | Interaction with PLZF abrogates c-myc repression | Increased cell proliferation, apoptosis abrogation | Denne et al., 2007 | |
| Interaction with TZFP and hSGT abrogates the repression of AR and AR-regulated genes (e.g., c-myc) | Increased cell proliferation, apoptosis abrogation, stimulation of Rec expression | Kaufmann et al., 2010; Hanke et al., 2013a | |||
| Np9 | Germ cell | Interaction with PLZF abrogates c-myc repression | Increased cell proliferation, apoptosis abrogation | Denne et al., 2007 | |
| – | Interaction with LNX ubiquitin ligase | Perturbation of Numb/Notch pathway | Armbruester et al., 2004 | ||
| – | Interaction with MDM2 ubiquitin ligase | Reduced MDM2-mediated proteasomal degradation of p53 | Heyne et al., 2015 | ||
| Lymphoma (EBV-transformed B cells) | Interaction with EBV EBNA2 | Downregulation of viral promoter activation and transcription factors binding | Gross et al., 2011 | ||
| Leukemia | Upregulation of pERK, c-Myc, β-catenin and Notch1 | Increased cell proliferation, faster and increased tumor growth | Chen et al., 2013 |
HERV-derived Env proteins for which a specific pro-oncogenic activity and/or a precise effect on cellular transformation have been characterized are included.