Evidence map›Paper›PMID 25238333›Full record

ArticleOncotarget2014

P2Y2R activation by nucleotides released from the highly metastatic breast cancer cell MDA-MB-231 contributes to pre-metastatic niche formation by mediating lysyl oxidase secretion, collagen crosslinking, and monocyte recruitment.

Young Nak Joo, Hana Jin, So Young Eun, Sang Won Park, Ki Churl Chang, Hye Jung Kim

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

47 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. Review
  3. P2YInternational journal of molecular sciences · 2025
    Review
  4. Article
  5. Review
  6. Review
  7. P2YPurinergic signalling · 2025
    Article
  8. Premetastatic niche mechanics and organotropism in breast cancer.npj biological physics and mechanics · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Therapeutic potential for P2YPurinergic signalling · 2023
    Review
  14. Article
  15. Review
  16. Review
  17. Review
  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

6 authors at 1 institution in 1 country.

Young Nak JooDepartment of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Hana JinDepartment of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
So Young EunDepartment of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Sang Won ParkDepartment of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Ki Churl ChangDepartment of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Hye Jung KimDepartment of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Gyeongsang National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor microenvironmental hypoxia induces hypoxia inducible factor-1α (HIF-1α) overexpression, leading to the release of lysyl oxidase (LOX), which crosslinks collagen at distant sites to facilitate environmental changes that allow cancer cells to easily metastasize. Our previous study showed that activation of the P2Y2 receptor (P2Y2R) by ATP released from MDA-MB-231 cells increased MDA-MB-231 cell invasion through endothelial cells. Therefore, in this study, we investigated the role of P2Y2R in breast cancer cell metastasis to distant sites. ATP or UTP released from hypoxia-treated MDA-MB-231 cells induced HIF-1α expression and LOX secretion by the activation of P2Y2R, and this phenomenon was significantly reduced in P2Y2R-depleted MDA-MB-231 cells. Furthermore, P2Y2R-mediated LOX release induced collagen crosslinking in an in vitro model. Finally, nude mice injected with MDA-MB-231 cells showed high levels of LOX secretion, crosslinked collagen and CD11b+ BMDC recruitment in the lung; however, mice that were injected with P2Y2R-depleted MDA-MB-231 cells did not exhibit these changes. These results demonstrate that P2Y2R plays an important role in activation of the HIF-1α-LOX axis, the induction of collagen crosslinking and the recruitment of CD11b+ BMDCs. Furthermore, P2Y2R activation by nucleotides recruits THP-1 monocytes, resulting in primary tumor progression and pre-metastatic niche formation.

Indexed as

AnimalsBreast NeoplasmsCD11b AntigenCell HypoxiaCell Line, TumorCell MovementCollagenDisease ProgressionEndothelial CellsEnzyme ActivationFemaleGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitMacrophagesMCF-7 CellsCD11b AntigenCollagenCTRL protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitITGAM protein, humanNucleotidesProtein-Lysine 6-OxidaseReceptors, Purinergic P2Y2RNA, Small InterferingSerine Endopeptidases

Identifiers

PMID25238333
PMCPMC4253437
OpenAlexW2160191376

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.