ArticlemBio2019
Repression of Human Papillomavirus Oncogene Expression under Hypoxia Is Mediated by PI3K/mTORC2/AKT Signaling.
Article in mBio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- Recent progress and therapeutic strategies in the treatment of cervical neuroendocrine neoplasms (Review).International journal of molecular medicine · 2026Review
- Lipid reprogramming of stratified squamous epithelium by the high-risk HPV E6 and E6/E7 oncoproteins.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Th17 cells favor migration and invasiveness of cervical cancer cells under hypoxia in an IGF2BP2-dependent manner.International journal of cancer · 2026Article
- Intratumoral spatiotemporal heterogeneity of HPV DNA status in HPV-associated oropharyngeal squamous cell carcinoma with clinical record.Journal of translational medicine · 2026Article
- An Overview of the Mechanisms of HPV-Induced Cervical Cancer: The Role of Kinase Targets in Pathogenesis and Drug Resistance.Cancers · 2026Review
- Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16Exploration of targeted anti-tumor therapy · 2026Article
- Hypoxia drives cervical cancer progression via OCT4/ORAI3-dependent glycolysis and CaCellular and molecular life sciences : CMLS · 2025Article
- RNA sequencing and bioinformatics analysis have identifiedTranslational cancer research · 2025Article
- Hypoxic HPV-Positive Cancer Cells Are Particularly Sensitive to the Pro-Senescent Effects of B-MYB Repression Due to the Lack of Compensatory A-MYB Induction.Journal of medical virology · 2025Article
- Pleiotropic Effects of Metformin on the Chemotherapy Response of HPV-Positive Cancer Cells.Journal of medical virology · 2025Article
- The ability of clostridium novyi-NT spores to induce apoptosis via the mitochondrial pathway in mice with HPV-positive cervical cancer tumors derived from the TC-1 cell line.BMC complementary medicine and therapies · 2024Article
- Molecular aspects of cervical cancer: a pathogenesis update.Frontiers in oncology · 2024Review
- The potential role of HPV oncoproteins in the PD-L1/PD-1 pathway in cervical cancer: new perspectives on cervical cancer immunotherapy.Frontiers in oncology · 2024Review
- Anti-tumor Effects of Cisplatin Synergist in Combined Treatment withAdvanced pharmaceutical bulletin · 2023Article
- Article
- PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.Biology · 2023Review
- Insight into Oncogenic Viral Pathways as Drivers of Viral Cancers: Implication for Effective Therapy.Current oncology (Toronto, Ont.) · 2023Review
- Functions and modulation of PKM2 activity by human papillomavirus E7 oncoprotein (Review).Oncology letters · 2023Review
- The neuroprotective effects of Liuwei Dihuang medicine in the APP/PS1 mouse model are dependent on the PI3K/Akt signaling pathway.Frontiers in pharmacology · 2023Article
- HPV and radiosensitivity of cervical cancer: a narrative review.Annals of translational medicine · 2022Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is linked to therapeutic resistance and poor clinical prognosis for many tumor entities, including human papillomavirus (HPV)-positive cancers. Notably, HPV-positive cancer cells can induce a dormant state under hypoxia, characterized by a reversible growth arrest and strong repression of viral E6/E7 oncogene expression, which could contribute to therapy resistance, immune evasion and tumor recurrence. The present work aimed to gain mechanistic insights into the pathway(s) underlying HPV oncogene repression under hypoxia. We show that E6/E7 downregulation is mediated by hypoxia-induced stimulation of AKT signaling. Ablating AKT function in hypoxic HPV-positive cancer cells by using chemical inhibitors efficiently counteracts E6/E7 repression. Isoform-specific activation or downregulation of AKT1 and AKT2 reveals that both AKT isoforms contribute to hypoxic E6/E7 repression and act in a functionally redundant manner. Hypoxic AKT activation and consecutive E6/E7 repression is dependent on the activities of the canonical upstream AKT regulators phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR) complex 2 (mTORC2). Hypoxic downregulation of E6/E7 occurs, at least in part, at the transcriptional level. Modulation of E6/E7 expression by the PI3K/mTORC2/AKT cascade is hypoxia specific and not observed in normoxic HPV-positive cancer cells. Quantitative proteome analyses identify additional factors as candidates to be involved in hypoxia-induced activation of the PI3K/mTORC2/AKT signaling cascade and in the AKT-dependent repression of the E6/E7 oncogenes under hypoxia. Collectively, these data uncover a functional key role of the PI3K/mTORC2/AKT signaling cascade for viral oncogene repression in hypoxic HPV-positive cancer cells and provide new insights into the poorly understood cross talk between oncogenic HPVs and their host cells under hypoxia.
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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.