Evidence map›Paper›PMID 28253371›Full record

ArticlePLoS pathogens2017

Autophagy regulates UBC9 levels during viral-mediated tumorigenesis.

Domenico Mattoscio, Chiara Casadio, Claudia Miccolo, Fausto Maffini, Andrea Raimondi, Carlo Tacchetti, Tarik Gheit, Marta Tagliabue, Viviana E Galimberti, Francesca De Lorenzi and 5 more

Open access · goldAbstract read
In one paragraph

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 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. UBC9: a novel therapeutic target in papillary thyroid carcinoma.Journal of endocrinological investigation · 2025
    Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
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  11. Review
  12. Article
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  14. Article
  15. Article
  16. Article
  17. Review
  18. HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022
    Article
  19. Post-Translational Modification of Lamins: Mechanisms and Functions.Frontiers in cell and developmental biology · 2022
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

Domenico MattoscioEuropean Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Chiara CasadioEuropean Institute of Oncology, Department of Pathology, Milan, Italy.
Claudia MiccoloEuropean Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Fausto MaffiniEuropean Institute of Oncology, Department of Pathology, Milan, Italy.
Andrea RaimondiExperimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Carlo TacchettiExperimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Tarik GheitInfections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France.
Marta TagliabueEuropean Institute of Oncology, Division of Otolaryngology and Head and Neck Surgery, Milan, Italy.
Viviana E GalimbertiEuropean Institute of Oncology Senology Division, Milan, Italy.
Francesca De LorenziEuropean Institute of Oncology, Plastic Surgery Department, Milan, Italy.
Michael PawlitaDivision of Molecular Diagnostics of Oncogenic Infections, Research Program Infection, Inflammation and Cancer, German Cancer Research Center, Heidelberg, Germany.ORCID 0000-0002-4720-8306
Fausto ChiesaEuropean Institute of Oncology, Division of Otolaryngology and Head and Neck Surgery, Milan, Italy.
Mohssen AnsarinEuropean Institute of Oncology, Division of Otolaryngology and Head and Neck Surgery, Milan, Italy.
Massimo TommasinoInfections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France.
Susanna ChioccaEuropean Institute of Oncology, Department of Experimental Oncology, Milan, Italy.ORCID 0000-0002-9721-0850
European Institute of Oncology · ITCentre international de recherche sur le cancer · FRVita-Salute San Raffaele University · ITGerman Cancer Research Center · DE

Funding

World Health Organization 001
6 · The paper itself

Abstract

UBC9, the sole E2-conjugating enzyme required for SUMOylation, is a key regulator of essential cellular functions and, as such, is frequently altered in cancers. Along these lines, we recently reported that its expression gradually increases during early stages of human papillomavirus (HPV)-mediated cervical lesions transformation. However, a better understanding of how UBC9 is exploited by transforming viral oncoproteins is still needed. In the present study, we show that in human samples HPV drives UBC9 up-regulation also in very early steps of head and neck tumorigenesis, pointing to the important role for UBC9 in the HPV-mediated carcinogenic program. Moreover, using HPV-infected pre-cancerous tissues and primary human keratinocytes as the natural host of the virus, we investigate the pathological meaning and the cellular mechanisms responsible for UBC9 de-regulation in an oncoviral context. Our results show that UBC9 overexpression is promoted by transforming viral proteins to increase host cells' resistance to apoptosis. In addition, ultrastuctural, pharmacological and genetic approaches crucially unveil that UBC9 is physiologically targeted by autophagy in human cells. However, the presence of HPV E6/E7 oncoproteins negatively impacts the autophagic process through selective inhibition of autophagosome-lysosome fusion, finally leading to p53 dependent UBC9 accumulation during viral-induced cellular transformation. Therefore, our study elucidates how UBC9 is manipulated by HPV oncoproteins, details the physiological mechanism by which UBC9 is degraded in cells, and identifies how HPV E6/E7 impact on autophagy. These findings point to UBC9 and autophagy as novel hallmarks of HPV oncogenesis, and open innovative avenues towards the treatment of HPV-related malignancies.

Indexed as

ApoptosisAutophagyCell Transformation, NeoplasticCell Transformation, ViralFemaleFlow CytometryHumansImmunoblottingImmunohistochemistryMicroscopy, ConfocalOncogene Proteins, ViralPapillomaviridaePapillomavirus InfectionsPolymerase Chain ReactionTransduction, GeneticTransfectionOncogene Proteins, ViralUbiquitin-Conjugating EnzymesUbiquitin-Conjugating Enzyme UBC9

Identifiers

PMID28253371
PMCPMC5349695
OpenAlexW2592591707

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.