ArticlePLoS pathogens2017
A human endogenous retrovirus-derived gene that can contribute to oncogenesis by activating the ERK pathway and inducing migration and invasion.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches.International journal of molecular sciences · 2022Pooled it
- Human Endogenous Retroviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Emerging Roles in Pathogenesis, Immunity, Biomarkers and Therapeutics.International journal of molecular sciences · 2026Review
- HERV6196 as an enhancer with oncogenic potential in rectal cancer.Microbiology spectrum · 2026Article
- Plasma HERV-K envelopE RNA: a minimally invasive biomarker for lung adenocarcinoma detection and prognostic assessment in the context of conventional serum tumor markers.Frontiers in immunology · 2026Article
- Oncogenic role of ERV with therapeutic potential.Frontiers in immunology · 2026Review
- Locus-specific HERV expression identifies an aggressive, NK-depleted, checkpoint-refractory acral melanoma phenotype.Frontiers in medicine · 2026Article
- Characterization of HERV-K (HML-2) Rec proteins encoded in the human genome and their post-transcriptional function.Journal of virology · 2025Article
- Human Endogenous Retroviruses and Diseases.MedComm · 2025Review
- Metagenomic fingerprints in bronchoalveolar lavage differentiate pulmonary diseases.NPJ digital medicine · 2025Article
- Human endogenous retrovirus K (HERV-K) envelope structures in pre- and postfusion by cryo-EM.Science advances · 2025Article
- Discovery of KRAS(G12D) selective degrader ASP3082.Communications chemistry · 2025Article
- Review
- Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons.Nature communications · 2025Article
- The Role of Human Endogenous Retroviruses in the Initiation and Progression of Melanoma.Biomedicines · 2025Review
- Human endogenous retrovirus-K envelope protein is aberrantly expressed in serous ovarian cancer and promotes chemosensitivity via NF-κB/P-glycoprotein pathway inhibition.Journal of ovarian research · 2025Article
- An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis.Nucleic acids research · 2025Article
- Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy.International journal of biological sciences · 2025Review
- Human Endogenous Retroviruses Expression in Autoimmunity.The Yale journal of biology and medicine · 2024Review
- Epigenetic regulation of HERVs: Implications for cancer immunotherapy.Genes & genomics · 2024Review
- Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endogenous retroviruses are cellular genes of retroviral origin captured by their host during the course of evolution and represent around 8% of the human genome. Although most are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins. Among these, the HERV-K(HML2) family is remarkable since its members have amplified relatively recently and many of them still have full length coding genes. Furthermore, they are induced in cancers, especially in melanoma, breast cancer and germ cell tumours, where viral particles, as well as the envelope protein (Env), can be detected. Here we show that HERV-K(HML2) Env per se has oncogenic properties. Its expression in a non-tumourigenic human breast epithelial cell line induces epithelial to mesenchymal transition (EMT), often associated with tumour aggressiveness and metastasis. In our model, this is typified by key modifications in a set of molecular markers, changes in cell morphology and enhanced cell motility. Remarkably, microarrays performed in 293T cells reveal that HERV-K(HML2) Env is a strong inducer of several transcription factors, namely ETV4, ETV5 and EGR1, which are downstream effectors of the MAPK ERK1/2 and are associated with cellular transformation. We demonstrate that HERV-K(HML2) Env effectively activates the ERK1/2 pathway in our experimental setting and that this activation depends on the Env cytoplasmic tail. In addition, this phenomenon is very specific, being absent with every other retroviral Env tested, except for Jaagsiekte Sheep Retrovirus (JSRV) Env, which is already known to have transforming properties in vivo. Though HERV-K Env is not directly transforming by itself, the newly discovered properties of this protein may contribute to oncogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.