Evidence map›Paper›PMID 26876212›Full record

ArticleOncogene2016

Overexpression of PIK3CA in murine head and neck epithelium drives tumor invasion and metastasis through PDK1 and enhanced TGFβ signaling.

L Du, X Chen, Y Cao, L Lu, F Zhang, S Bornstein, Y Li, P Owens, S Malkoski, S Said and 5 more

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

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  19. PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021
    Review
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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

15 authors at 3 institutions in 2 countries.

L DuDepartment of Otolaryngology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
X ChenDepartment of Otolaryngology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Y CaoDepartment of Otolaryngology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
L LuDepartment of Otolaryngology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
F ZhangDepartment of Otolaryngology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
S BornsteinDepartment of Otolaryngology, Oregon Health and Science University, Portland, OR, USA.
Y LiDepartment of Otolaryngology, Oregon Health and Science University, Portland, OR, USA.
P OwensDepartment of Otolaryngology, Oregon Health and Science University, Portland, OR, USA.
S MalkoskiDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
S SaidDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
F JinDepartment of Surgical Oncology, The First University Hospital of China Medical University, Shengyang, Liaoning, China.
M Kulesz-MartinDepartment of Dermatology, Oregon Health and Science University, Portland, OR, USA.
N GrossDepartment of Otolaryngology, Oregon Health and Science University, Portland, OR, USA.
X-J WangDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
S-L LuDepartment of Otolaryngology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
University of Colorado Anschutz Medical Campus · USOregon Health & Science University · USFirst Hospital of China Medical University · CN

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Transgenic and Gene Targeting CoreP30AR057212 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI KOCH, PETER J. · 2009 to 2018
$6.2M
Training in the Molecular Basis of Skin/Mucosa PathobiologyT32CA106195 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI KULESZ-MARTIN, MOLLY F. · 2004 to 2018
$3.8M
Illuminating molecular targetable pathways in HNSCCR01CA192405 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI MCWEENEY, SHANNON K. · 2015 to 2019
$2.5M
The Role of PI3K Pathway in Head and Neck Cancer Invasion and MetastasisR01DE021788 · NIDCR · UNIVERSITY OF COLORADO DENVER · PI LU, SHI-LONG · 2011 to 2015
$1.8M
TGFbeta and lung squamous cell carcinomaK08CA131483 · NCI · UNIVERSITY OF COLORADO DENVER · PI MALKOSKI, STEPHEN P · 2008 to 2012
$685k
Targeting defective DNA pathways in Smad4 deficient lung cancerR21CA194662 · NCI · UNIVERSITY OF COLORADO DENVER · PI MALKOSKI, STEPHEN P · 2015 to 2016
$372k
NCI NIH HHS K08 CA131483NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA192405NCI NIH HHS R21 CA194662NCI NIH HHS T32 CA106195NIAMS NIH HHS P30 AR057212NIDCR NIH HHS R01 DE021788
6 · The paper itself

Abstract

Head and neck squamous cell carcinoma (HNSCC) patients have a poor prognosis, with invasion and metastasis as major causes of mortality. The phosphatidylinositol 3-kinase (PI3K) pathway regulates a wide range of cellular processes crucial for tumorigenesis, and PIK3CA amplification and mutation are among the most common genetic alterations in human HNSCC. Compared with the well-documented roles of the PI3K pathway in cell growth and survival, the roles of the PI3K pathway in tumor invasion and metastasis have not been well delineated. We generated a PIK3CA genetically engineered mouse model (PIK3CA-GEMM) in which wild-type PIK3CA is overexpressed in head and neck epithelium. Although PIK3CA overexpression alone was not sufficient to initiate HNSCC formation, it significantly increased tumor susceptibility in an oral carcinogenesis mouse model. PIK3CA overexpression in mouse oral epithelium increased tumor invasiveness and metastasis by increasing epithelial-mesenchymal transition and by enriching a cancer stem cell phenotype in tumor epithelial cells. In addition to these epithelial alterations, we also observed marked inflammation in tumor stroma. AKT is a central signaling mediator of the PI3K pathway. However, molecular analysis suggested that progression of PIK3CA-driven HNSCC is facilitated by 3-phosphoinositide-dependent protein kinase (PDK1) and enhanced transforming growth factor β (TGFβ) signaling rather than by AKT. Examination of human HNSCC clinical samples revealed that both PIK3CA and PDK1 protein levels correlated with tumor progression, highlighting the significance of this pathway. In summary, our results offer significant insight into how PIK3CA overexpression drives HNSCC invasion and metastasis, providing a rationale for targeting PI3K/PDK1 and TGFβ signaling in advanced HNSCC patients with PIK3CA amplification.

Indexed as

AnimalsAnimals, Genetically ModifiedCell ProliferationCell Transformation, NeoplasticClass I Phosphatidylinositol 3-KinasesDisease Models, AnimalEpithelial-Mesenchymal TransitionEpitheliumFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansLymphatic MetastasisMaleMiceMutationClass I Phosphatidylinositol 3-KinasesPDK1 protein, humanPdk1 protein, mousePhosphatidylinositol 3-KinasesPik3ca protein, mouseProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinaseTransforming Growth Factor beta

Identifiers

PMID26876212
PMCPMC4985507
OpenAlexW2285950721

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.