Evidence map›Paper›PMID 29901191›Full record

ArticleInternational journal of oncology2018

E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells.

Jiaoe Chen, Chaoju Gong, Huiqin Mao, Zhaoyun Li, Zejun Fang, Qiang Chen, Min Lin, Xiang Jiang, Yanyan Hu, Wei Wang and 3 more

Open access · hybridAbstract read
In one paragraph

Article in International journal of oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

67 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. Review
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  4. Review
  5. Eutopic Endometrium Immune Changes Involved in Development and Progression of Endometriosis: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026
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  8. Review
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  10. The YYR (YY1- RKIP) Regulatory Axis in the pathogenesis of Cancer and Immune Evasion.Journal of experimental & clinical cancer research : CR · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. CD4Trends in cancer · 2024
    Review
  18. Article
  19. Review
  20. Article

7 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

13 authors at 3 institutions in 1 country.

Jiaoe ChenDepartment of Gastroenterology, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Chaoju GongXuzhou Key Laboratory of Ophthalmology, The First People's Hospital of Xuzhou, Xuzhou, Jiangsu 221002, P.R. China.
Huiqin MaoUltrasonography Department, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Zhaoyun LiClinical Laboratory, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, Zheijiang 318000, P.R. China.
Zejun FangCentral Laboratory, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Qiang ChenDepartment of Gastroenterology, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Min LinCentral Laboratory, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Xiang JiangDepartment of Gastroenterology, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Yanyan HuCentral Laboratory, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Wei WangCentral Laboratory, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Xiaomin ZhangPharmaceutical Preparation Section, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Xianjun ChenClinical Laboratory, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, Zheijiang 318000, P.R. China.
Hongzhang LiDepartment of Gastroenterology, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China.
Taizhou Central Hospital · CNTaizhou University · CNXuzhou Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Colorectal cancer (CRC) is a type of cancer with a mortality rate among the highest worldwide owing to its high rate of metastasis. Therefore, inflammation-associated metastasis in the development of CRC is currently a topic of considerable interest. In the present study, the pro-inflammatory cytokine interleukin-4 (IL-4) was identified to promote the epithelial-mesenchymal transition (EMT) of CRC cells. However, the enhancing effect of IL-4 was more evident in HCT116 cells compared with in RKO cells. Accordingly, an increased expression level of STAT6 was observed in HCT116 cells compared with RKO cells. Further investigations identified that E2F1 was required for maintaining the level of signal transducer and activator of transcription 6 (STAT6) in HCT116 cells. Mechanistically, E2F1 induced specificity protein 3 (SP3) directly by binding to the promoter of the STAT6 gene and activating its transcription in CRC cells. As a result, phosphorylation-activated STAT6 increased the expression of several EMT drivers, including zinc finger E-box-binding homeobox (Zeb)1 and Zeb2, which serve a critical function in IL-4-induced EMT. Rescue experiments further confirmed that IL-4-induced EMT relied on an intact E2F1/SP3/STAT6 axis in CRC cells. Finally, analysis of clinical CRC specimens revealed a positive correlation between E2F1, SP3 and STAT6. The ectopically expressed E2F1/SP3/STAT6 axis indicated a poor prognosis in patients with CRC. In conclusion, the E2F1/SP3/STAT6 pathway was identified to be essential for IL-4 signaling-induced EMT and aggressiveness of CRC cells.

Indexed as

AnimalsCell ProliferationColorectal NeoplasmsE2F1 Transcription FactorEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHCT116 CellsHT29 CellsHumansInterleukin-4MaleMiceNeoplasm TransplantationPromoter Regions, GeneticSignal TransductionE2F1 protein, humanE2F1 Transcription FactorIL4 protein, humanInterleukin-4SP3 protein, humanSp3 Transcription FactorSTAT6 protein, humanSTAT6 Transcription Factor

Identifiers

PMID29901191
PMCPMC6017240
OpenAlexW2805609630

What OpenQuestion holds

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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.