Evidence map›Paper›PMID 24046371›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Tumor suppressor p16INK4A is necessary for survival of cervical carcinoma cell lines.

Margaret E McLaughlin-Drubin, Donglim Park, Karl Munger

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 4 pooled it
9.0field-weighted citation impact, top 2% 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

106 citing papers in PubMed, 4 syntheses or guidelines pooled it, 172 citations in OpenAlex.

  1. Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2016
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46 more citing papers are in PubMed but not listed here.

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

3 authors at 2 institutions in 2 countries.

Margaret E McLaughlin-DrubinDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115.
Donglim Park
Karl Munger
Brigham and Women's Hospital · USInstitute of Virology of the Slovak Academy of Sciences · SK

Funding

BIOLOGICAL ACTIVITY OF HPV E7 IN HUMAN EPITHELIAL CELLSR01CA066980 · NCI · TUFTS UNIVERSITY BOSTON · PI MUNGER, KARL · 1996 to 2019
$7.4M
Epigenetic Reprogramming by the Human Papillomavirus E7 OncoproteinK01CA143010 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI MCLAUGHLIN-DRUBIN, MARGARET ERIN · 2010 to 2012
$421k
NCI NIH HHS K01 CA143010NCI NIH HHS K01CA143010NCI NIH HHS R01 CA066980NCI NIH HHS R01CA066980
6 · The paper itself

Abstract

The tumor suppressor p16(INK4A) inhibits formation of enzymatically active complexes of cyclin-dependent kinases 4 and 6 (CDK4/6) with D-type cyclins. Oncogenic stress induces p16(INK4A) expression, which in turn triggers cellular senescence through activation of the retinoblastoma tumor suppressor. Subversion of oncogene-induced senescence is a key step during cancer development, and many tumors have lost p16(INK4A) activity by mutation or epigenetic silencing. Human papillomavirus (HPV)-associated tumors express high levels of p16(INK4A) in response to E7 oncoprotein expression. Induction of p16(INK4A) expression is not a consequence of retinoblastoma tumor suppressor inactivation but is triggered by a cellular senescence response and is mediated by epigenetic derepression through the H3K27-specific demethylase (KDM)6B. HPV E7 expression causes an acute dependence on KDM6B expression for cell survival. The p16(INK4A) tumor suppressor is a critical KDM6B downstream transcriptional target and its expression is critical for cell survival. This oncogenic p16(INK4A) activity depends on inhibition of CDK4/CDK6, suggesting that in cervical cancer cells where retinoblastoma tumor suppressor is inactivated, CDK4/CDK6 activity needs to be inhibited in order for cells to survive. Finally, we note that HPV E7 expression creates a unique cellular vulnerability to small-molecule KDM6A/B inhibitors.

Indexed as

CarcinomaCell Line, TumorCell SurvivalCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p16FemaleHumansJumonji Domain-Containing Histone DemethylasesPapillomavirus E7 ProteinsReal-Time Polymerase Chain ReactionRNA InterferenceTumor Suppressor ProteinsUterine Cervical NeoplasmsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p16Jumonji Domain-Containing Histone DemethylasesKDM6B protein, humanoncogene protein E7, Human papillomavirus type 16Papillomavirus E7 ProteinsTumor Suppressor Proteinsapoptosisbiomarkercancer therapysynthetic lethality

Identifiers

PMID24046371
PMCPMC3791710
OpenAlexW1974915741

What OpenQuestion holds

Textmetadata
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.