Evidence map›Paper›PMID 31958486›Full record

ArticleCancer letters2020

Human papillomavirus insertions identify the PIM family of serine/threonine kinases as targetable driver genes in head and neck squamous cell carcinoma.

Tatevik R Broutian, Bo Jiang, Jingfeng Li, Keiko Akagi, Shanying Gui, Zhengqiu Zhou, Weihong Xiao, David E Symer, Maura L Gillison

Open access · greenAbstract read
In one paragraph

Article in Cancer letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
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  6. Relationship between the transcriptional expression of PIM1 and local control in patients with head and neck squamous cell carcinomas treated with radiotherapy.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 · 2022
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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

9 authors at 2 institutions in 1 country.

Tatevik R BroutianBiomedical Sciences Graduate Program, Ohio State University, Columbus, OH, 43210, United States.
Bo JiangDepartment of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States.
Jingfeng LiDivision of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, OH, 43210, United States.
Keiko AkagiDepartment of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States.
Shanying GuiDivision of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, OH, 43210, United States.
Zhengqiu ZhouDivision of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, OH, 43210, United States.
Weihong XiaoDepartment of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States.
David E SymerDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States. Electronic address: desymer@mdanderson.org.
Maura L GillisonDepartment of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, United States. Electronic address: mgillison@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USThe Ohio State University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Daniel G. Stover · 1985 to 2026
$132.3M
Dr. Keiko Akagi, A Bioinformatics Specialist in Cancer Genomics Research at OSU Comprehensive Cancer CenterR50CA211533 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AKAGI, KEIKO · 2016 to 2020
$608k
NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA016672NCI NIH HHS R50 CA211533
6 · The paper itself

Abstract

Human papillomavirus (HPV) insertions in cancer genomes have been linked to various forms of focal genomic instability and altered expression of neighboring genes. Here we tested the hypothesis that investigation of HPV insertions in a head and neck cancer squamous cell carcinoma (HNSCC) cell line would identify targetable driver genes contributing to oncogenesis of other HNSCC. In the cell line UPCI:SCC090 HPV16 integration amplified the PIM1 serine/threonine kinase gene ~16-fold, thereby increasing transcript and protein levels. We used genetic and pharmacological approaches to inhibit PIM kinases in this and other HNSCC cell lines. Knockdown of PIM1 transcripts by transfected short hairpin RNAs reduced UPCI:SCC090 viability. CRISPR/Cas9-mediated mutagenesis of PIM1 caused cell cycle arrest and apoptosis. Pharmacological inhibition of PIM family kinases decreased growth of UPCI:SCC090 and additional HNSCC cell lines in vitro and a xenograft UPCI:SCC090 model in vivo. Based on established interactions between intracellular signaling pathways and relatively high levels of gene expression in almost all HNSCC, we also evaluated combinations of PIM kinase and epidermal growth factor receptor (EGFR) inhibitors. Dual inhibition of these pathways resulted in supra-additive cell death. These data support clinical testing of PIM inhibitors alone or in combination in HNSCC.

Indexed as

AnimalsApoptosisCell ProliferationFemaleHead and Neck NeoplasmsHuman papillomavirus 16HumansMiceMice, NudePapillomavirus InfectionsPrognosisProto-Oncogene Proteins c-pim-1Squamous Cell Carcinoma of Head and NeckTumor Cells, CulturedVirus IntegrationXenograft Model Antitumor AssaysPIM1 protein, humanProto-Oncogene Proteins c-pim-1Head and neck squamous cell carcinomaHuman papillomavirus (HPV)Molecular therapeuticsPIM serine/threonine kinasesVirus insertional mutagenesis

Identifiers

PMID31958486
PMCPMC7239795
OpenAlexW2999036532

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.