ArticleThe Journal of clinical investigation2023
Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Endogenous retrovirus control of calbindin is essential for human early embryogenesis.Science advances · 2026Article
- Review
- Cellular senescence in lung cancer immune microenvironment and senotherapeutic opportunities.iScience · 2026Review
- Analysis of HERV-K (HML2) Expression in Colorectal Cancer Samples.Epigenomes · 2026Article
- TEITbase: a database for transposable element (TE)-initiated transcripts in human cancers.Database : the journal of biological databases and curation · 2026Article
- CDK9 Inhibition with enitociclib reveals influence on HERV and LINE RNA abundances in whole blood, T-, and B-Cell lines.BMC medical genomics · 2026Article
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- Endogenous retroviruses in aging and cancer: from genomic defense to oncogenic activation.Mobile DNA · 2025Review
- The expression, regulation, and function of human endogenous retroviruses in genitourinary cancers.Cell death discovery · 2025Review
- Article
- Co-option of an endogenous retrovirus (LTR7-HERVH) in early human embryogenesis: becoming useful and going unnoticed.Mobile DNA · 2025Review
- Primate retroelement exonization and sexually dimorphicScience immunology · 2025Article
- Retroelement co-option disrupts the cancer transcriptional programme.Genome medicine · 2025Article
- Review
- Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer.Science advances · 2024Article
- Activation of human endogenous retroviruses and its physiological consequences.Nature reviews. Molecular cell biology · 2024Review
- Exploring HERV-K (HML-2) Influence in Cancer and Prospects for Therapeutic Interventions.International journal of molecular sciences · 2023Review
- The transcriptional landscape of endogenous retroelements delineates esophageal adenocarcinoma subtypes.NAR cancer · 2023Article
- Staring at the onco-exaptation: the two-faced medley of an ancient retrovirus, HERVH.The Journal of clinical investigation · 2023Article
- From Junk DNA to Genomic Treasure: Impacts of Transposable Element DNA, RNA, and Protein in Mammalian Development and Disease.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
Increased levels and diversity of human endogenous retrovirus (HERV) transcription characterize most cancer types and are linked with disease outcomes. However, the underlying processes are incompletely understood. Here, we show that elevated transcription of HERVH proviruses predicted survival of lung squamous cell carcinoma (LUSC) and identified an isoform of CALB1, encoding calbindin, ectopically driven by an upstream HERVH provirus under the control of KLF5, as the mediator of this effect. HERVH-CALB1 expression was initiated in preinvasive lesions and associated with their progression. Calbindin loss in LUSC cell lines impaired in vitro and in vivo growth and triggered senescence, consistent with a protumor effect. However, calbindin also directly controlled the senescence-associated secretory phenotype (SASP), marked by secretion of CXCL8 and other neutrophil chemoattractants. In established carcinomas, CALB1-negative cancer cells became the dominant source of CXCL8, correlating with neutrophil infiltration and worse prognosis. Thus, HERVH-CALB1 expression in LUSC may display antagonistic pleiotropy, whereby the benefits of escaping senescence early during cancer initiation and clonal competition were offset by the prevention of SASP and protumor inflammation at later stages.
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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.