Evidence map›Paper›PMID 33491747›Full record

ArticleInternational journal of oncology2021

Reciprocal activation of HEY1 and NOTCH4 under SOX2 control promotes EMT in head and neck squamous cell carcinoma.

Takahito Fukusumi, Theresa W Guo, Shuling Ren, Sunny Haft, Chao Liu, Akihiro Sakai, Mizuo Ando, Yuki Saito, Sayed Sadat, Joseph A Califano

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

Article in International journal of oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 43% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

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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

10 authors at 3 institutions in 2 countries.

Takahito FukusumiMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Theresa W GuoMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Shuling RenMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Sunny HaftMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Chao LiuMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Akihiro SakaiDepartment of Otolaryngology‑Head and Neck Surgery, Tokai University, School of Medicine, Isehara, Kanagawa 259‑1193, Japan.
Mizuo AndoDepartment of Otolaryngology‑Head and Neck Surgery, University of Tokyo, Tokyo 113‑8655, Japan.
Yuki SaitoDepartment of Otolaryngology‑Head and Neck Surgery, University of Tokyo, Tokyo 113‑8655, Japan.
Sayed SadatMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Joseph A CalifanoMoores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
University of California, San Diego · USThe University of Tokyo · JPTokai University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Several comprehensive studies have demonstrated that the NOTCH pathway is altered in a bimodal manner in head and neck squamous cell carcinoma (HNSCC). In a previous study, it was found that the NOTCH4/HEY1 pathway was specifically upregulated in HNSCC and promoted epithelial‑mesenchymal transition (EMT), and that HEY1 activation supported SOX2 expression. However, the interactions in this pathway have not yet been fully elucidated. The present study investigated the NOTCH4/HEY1/SOX2 axis in HNSCC using in vitro models and the Cancer Genome Atlas (TCGA) database. To explore the association, reporter and ChIP RT‑qPCR assays using SOX2‑overexpressing (SOX2‑OE) cells were performed. The association between NOTCH4 and HEY1 was examined in the same manner using HEY1‑overexpressing (HEY1‑OE) cells. The results of the in vitro experiments indicated that HEY1 promoted EMT in the HNSCC cells. Furthermore, the overexpression of HEY1 also promoted sphere formation and increased murine xenograft tumorigenicity. Reporter assays and ChIP RT‑qPCR experiments indicated that SOX2 regulated HEY1 expression via direct binding of the HEY1 promoter. HEY1 expression significantly correlated with SOX2 expression in primary lung SCC and other SCCs using the TCGA database. HEY1 also regulated NOTCH4 expression to create a positive reciprocal feedback loop. On the whole, the present study demonstrates that HEY1 expression in HNSCC is regulated via the promotion of SOX2 and promotes EMT. The NOTCH4/HEY1 pathway is specifically upregulated via a positive reciprocal feedback loop mediated by the HEY1‑medaited regulation of NOTCH4 transcription, and SOX2 correlates with HEY1 expression in SCC from other primary sites.

Indexed as

AnimalsBasic Helix-Loop-Helix ProteinsCell Cycle ProteinsCell Line, TumorCell Transformation, NeoplasticDatasets as TopicEpithelial-Mesenchymal TransitionFeedback, PhysiologicalGene Expression Regulation, NeoplasticHumansMiceReceptor, Notch4Signal TransductionSOXB1 Transcription FactorsSpheroids, CellularSquamous Cell Carcinoma of Head and NeckBasic Helix-Loop-Helix ProteinsCell Cycle ProteinsHEY1 protein, humanNOTCH4 protein, humanReceptor, Notch4SOX2 protein, humanSOXB1 Transcription Factorshead and neck squamous cell carcinomaHEY1NOTCH4SOX2TCGA

Identifiers

PMID33491747
PMCPMC7864008
OpenAlexW3111526201

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.