Evidence map›Paper›PMID 30190462›Full record

ArticleNature communications2018

Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression.

Yuan Jiang, Yan-Yi Jiang, Jian-Jun Xie, Anand Mayakonda, Masaharu Hazawa, Li Chen, Jin-Fen Xiao, Chun-Quan Li, Mo-Li Huang, Ling-Wen Ding and 15 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed
8.3field-weighted citation impact, top 1% 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

145 citing papers in PubMed, 237 citations in OpenAlex.

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  12. Enhancer Reprogramming Reveals the Tumorigenic Role of PTPRZ1 in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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  14. MIAT promotes tumor-infiltrating CD8Journal for immunotherapy of cancer · 2025
    Article
  15. Review
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85 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

25 authors at 6 institutions in 4 countries.

Yuan JiangCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Yan-Yi JiangCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. jyy.36000@gmail.com.
Jian-Jun XieDepartment of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou, 515041, China.
Anand MayakondaCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Masaharu HazawaCell-Bionomics Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, 920-1192, Ishikawa, Japan.
Li ChenDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, 90048, USA.
Jin-Fen XiaoCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Chun-Quan LiSchool of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, 163319, China.
Mo-Li HuangCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Ling-Wen DingCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Qiao-Yang SunCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.ORCID http://orcid.org/0000-0002-9855-5586
Liang XuCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.ORCID http://orcid.org/0000-0002-2700-4840
Deepika KanojiaCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Maya JeitanyCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
Jian-Wen DengDepartment of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou, 515041, China.
Lian-Di LiaoInstitute of Oncologic Pathology, Medical College of Shantou University, Shantou, 515041, China.
Harmik J SoukiasianDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, 90048, CA, USA.
Benjamin P BermanCenter for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, 90048, CA, USA.ORCID http://orcid.org/0000-0002-2099-9005
Jia-Jie HaoState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Li-Yan XuInstitute of Oncologic Pathology, Medical College of Shantou University, Shantou, 515041, China.ORCID http://orcid.org/0000-0002-1618-4292
En-Min LiDepartment of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou, 515041, China.
Ming-Rong WangState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Xin-Gang BiDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
De-Chen LinDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, 90048, USA. dchlin11@gmail.com.
H Phillip KoefflerCancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.ORCID http://orcid.org/0000-0001-5839-9913
National University of Singapore · SGCedars-Sinai Medical Center · USShantou University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNHarbin Medical University · CNKanazawa University · JP

Funding

Ministry of Education - Singapore (MOE) MOE2014-T3-1-006National Natural Science Foundation of China (National Science Foundation of China) 81672786National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore) NMRC/STaR/0021/2014
6 · The paper itself

Abstract

Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. However, functional consequence of their frequent co-localization at super-enhancers remains incompletely understood. Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter. Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. These results together identify a SCC-specific DNA/RNA/protein complex which activates TP63/SOX2-CCAT1-EGFR cascade and promotes SCC tumorigenesis, advancing our understanding of transcription dysregulation in cancer biology mediated by master TFs and super-enhancers.

Indexed as

Enhancer Elements, GeneticAnimalsCarcinoma, Squamous CellCell Line, TumorErbB ReceptorsGene Expression Regulation, NeoplasticHumansMAP Kinase Kinase KinasesMice, Inbred NODPhosphatidylinositol 3-KinasesPromoter Regions, GeneticProto-Oncogene Proteins c-aktRNA, Long NoncodingSOXB1 Transcription FactorsTranscription FactorsTumor Suppressor ProteinsCCAT1 long noncoding RNA, humanEGFR protein, humanErbB ReceptorsMAP Kinase Kinase KinasesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, Long NoncodingSOX2 protein, humanSOXB1 Transcription FactorsTP63 protein, humanTranscription FactorsTumor Suppressor Proteins

Identifiers

PMID30190462
PMCPMC6127298
OpenAlexW2889051002

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.