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RESEARCH PRODUCT
Repression of Human Papillomavirus Oncogene Expression under Hypoxia Is Mediated by PI3K/mTORC2/AKT Signaling
Felix Hoppe-seylerArnulf MayerMitsugu ShimobayashiPrajakta KhalkarPrajakta KhalkarMatthias DürstStephen J. KraemerStephen J. KraemerBianca J. KuhnBianca J. KuhnFelicitas BosslerFelicitas BosslerSvenja AdrianSvenja AdrianKarin Hoppe-seylerClaudia LohreyThomas GüntherFrank RöslAdam GrundhoffAngela HolzerJeroen KrijgsveldJeroen Krijgsveldsubject
cervical cancerAKT1Down-RegulationAKT2Mechanistic Target of Rapamycin Complex 2mTORC2MicrobiologyHost-Microbe Biology03 medical and health sciences0302 clinical medicineVirologyCell Line TumorHumansHypoxiahuman papillomavirustumor virusPsychological repressionMechanistic target of rapamycinProtein kinase BPapillomaviridaePI3K/AKT/mTOR pathway030304 developmental biology0303 health sciencesOncogenebiologyAKTOncogene Proteins ViralQR1-502030220 oncology & carcinogenesisHost-Pathogen InteractionsCancer researchbiology.proteinddc:004Phosphatidylinositol 3-KinaseProto-Oncogene Proteins c-aktResearch ArticleSignal Transductiondescription
Oncogenic HPV types are major human carcinogens. Under hypoxia, HPV-positive cancer cells can repress the viral E6/E7 oncogenes and induce a reversible growth arrest. This response could contribute to therapy resistance, immune evasion, and tumor recurrence upon reoxygenation. Here, we uncover evidence that HPV oncogene repression is mediated by hypoxia-induced activation of canonical PI3K/mTORC2/AKT signaling. AKT-dependent downregulation of E6/E7 is only observed under hypoxia and occurs, at least in part, at the transcriptional level. Quantitative proteome analyses identify additional factors as candidates to be involved in AKT-dependent E6/E7 repression and/or hypoxic PI3K/mTORC2/AKT activation. These results connect PI3K/mTORC2/AKT signaling with HPV oncogene regulation, providing new mechanistic insights into the cross talk between oncogenic HPVs and their host cells.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-02-01 | mBio |