Evidence map›Paper›PMID 28481872›Full record

ArticleOncogene2017

Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization.

H Guo, Q Zhu, X Yu, S B Merugu, H B Mangukiya, N Smith, Z Li, B Zhang, H Negi, R Rong and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

32 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Spatial protein redistribution: wandering but not lost.Cellular and molecular life sciences : CMLS · 2025
    Review
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  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Potential Role of AGR2 for Mammalian Skin Wound Healing.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Review
  15. Construction and stable gene expression of AGR2xPD1 bi-specific antibody that enhances attachment betweenSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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 4 institutions in 2 countries.

H GuoSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Q ZhuSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
X YuDepartment of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
S B MeruguSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
H B MangukiyaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
N SmithDepartment of Molecular Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Z LiDepartment of Molecular Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
B ZhangSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
H NegiSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
R RongSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
K ChengDepartment of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Z WuSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
D LiSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Jiao Tong University · CNUniversity of Pittsburgh · USShanghai Pulmonary Hospital · CNShanghai Sixth People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The importance of the tumor microenvironment in targeted anticancer therapies has been well recognized. Various protein factors participate in the cross-talk between tumor cells and non-malignant cells. Anterior gradient-2 (AGR2) is overexpressed in diverse human adenocarcinomas and it exists in both intracellular and extracellular spaces. Although intracellular AGR2 has been intensively investigated, the function of secreted AGR2, especially its exact mechanism of action is still poorly understood. Here we report that the secreted AGR2 promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts by enhancing the activities of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2). Further study indicated that AGR2 directly binds to these extracellular signaling molecules, and enhances their homodimerization. The extracellular AGR2 activity can be blocked to reduce angiogenesis and inhibit tumor growth in vitro and in vivo by a monoclonal antibody targeting the AGR2 self-dimerization region, and combined treatment with bevacizumab produced maximum inhibition effect. In conclusion, our investigation reveals a mechanism that directly links the secreted AGR2 with extracellular signaling networks, and we propose that the secreted AGR2 is a blockable molecular target, which acts as a chaperon-like enhancer to VEGF and FGF2.

Indexed as

Angiogenesis InhibitorsAnimalsApoptosisBevacizumabCell ProliferationCells, CulturedFemaleFibroblast Growth Factor 2HumansHuman Umbilical Vein Endothelial CellsMiceMice, NudeMucoproteinsNeovascularization, PathologicOncogene ProteinsOvarian NeoplasmsAGR2 protein, humanAngiogenesis InhibitorsBevacizumabFibroblast Growth Factor 2MucoproteinsOncogene ProteinsProteinsVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID28481872
OpenAlexW2613610540

What OpenQuestion holds

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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.