Dataset Information

Repression of Human Papillomavirus Oncogene Expression under Hypoxia is Mediated by PI3K/mTORC2/AKT Signaling

ABSTRACT: Cornerstones of the regulatory phenomena observed in hypoxic HPV-positive cancer cells are: (i) hypoxia blocks E6/E7, an effect that can be counteracted by (ii) AKT inhibition and by (iii) high glucose supply. To gain further insights into the underlying regulatory circuits, mass spectrometry-based quantitative proteome analyses were performed comparing normoxic and hypoxic SiHa cells and assessing their response towards AKTi VIII and 25 mM glucose under hypoxia

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Cervix Carcinoma

SUBMITTER: Bianca Kuhn

LAB HEAD: Felix Hoppe-Seyler

PROVIDER: PXD011095 | Pride | 2019-02-18

REPOSITORIES: Pride

ACCESS DATA

Publications

Effects of Metformin on the virus/host cell crosstalk in human papillomavirus-positive cancer cells.

Hoppe-Seyler Karin K Herrmann Anja L AL Däschle Antonia A Kuhn Bianca J BJ Strobel Tobias D TD Lohrey Claudia C Bulkescher Julia J Krijgsveld Jeroen J Hoppe-Seyler Felix F

International journal of cancer 20210506 5

Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The viral E6/E7 oncogenes maintain the malignant growth of HPV-positive cancer cells. Targeted E6/E7 inhibition results in efficient induction of cellular senescence, which could be exploited for therapeutic purposes. Here we show that viral E6/E7 expression is strongly downregulated by Metformin in HPV-positive cervical cancer and head and neck cancer cells, both at the transcript and protein level. Metformin-induced ...[more]

PMID: 33844847

Publication: 1/2

Similar Datasets

Project description:Oxygen fluctuation during tissue remodeling imposes a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastomas are believed to possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. To identify adaptive response mechanism, we compared the effects of acute and chronic hypoxia versus oxygenation on stem-like glioblastoma (GS) cells. GS cell lines were established and propagated either under normoxia (21% O2) or hypoxia (1% O2) and subsequently exposed to acute normoxia or hypoxia, respectively. Gene expression profiling revealed that acute hypoxia predominantly induced metabolic pathways and cell cycle arrest, whereas chronic hypoxia activated neurodevelopmental processes. In particular, we found increased expression of glycolytic enzymes, especially of the preparatory phase of glycolysis, under acute hypoxia, whereas pentose phosphate pathway (PPP) enzymes were downregulated. The opposite was found for acute oxygenation of hypoxic GS cells. Findings were confirmed by qPCR and immunoblot analyses. Despite downregulation by hypoxia, expression of PPP enzymes is increased in GBMs compared to normal brain, whereas expression of hypoxia-inducible enzymes of the parallel preparatory phase of glycolysis is decreased. Immunohistochemistry revealed strong staining for PPP enzymes in the bulk of GBM tissue, especially in highly proliferative areas, but not in pseudopalisading (hypoxic) cells. Glycolytic enzymes displayed an inverse pattern. Mass spectrometric analysis using [1,2-13C2]-D-glucose showed reduced glucose flux through the PPP under hypoxia in favor of flux through glycolysis. Acute and chronic hypoxia increased cell migration but reduced proliferation, whereas normoxia had opposite effects. Our findings extend Warburg’s observations by showing that in most tumor cells the PPP, which supplies metabolites for biomass production, is favored over the parallel preparatory phase of glycolysis, but is suppressed under acute severe hypoxia, causing a switch to direct glycolysis to protect against hypoxic stress.

Dataset Information

Repression of Human Papillomavirus Oncogene Expression under Hypoxia is Mediated by PI3K/mTORC2/AKT Signaling

Publications

Effects of Metformin on the virus/host cell crosstalk in human papillomavirus-positive cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure