Evidence map›Paper›PMID 29523764›Full record

ArticleMolecular cancer research : MCR2018

ABCC1-Exported Sphingosine-1-phosphate, Produced by Sphingosine Kinase 1, Shortens Survival of Mice and Patients with Breast Cancer.

Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Wei-Ching Huang, Santiago Lima, Nitai C Hait, Aparna Maiti, Kumiko Kida, Krista P Terracina, Hiroshi Miyazaki and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer research : MCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Review
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  7. Review
  8. Article
  9. World journal of oncology · 2025
    Article
  10. Review
  11. Article
  12. Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Article
  15. Breast Cancer Chemoresistance: Insights into the Regulatory Role of lncRNA.International journal of molecular sciences · 2023
    Review
  16. Article
  17. Article
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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

18 authors at 6 institutions in 3 countries.

Akimitsu YamadaDivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Masayuki NagahashiDivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Tomoyoshi AoyagiDivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Wei-Ching HuangDivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Santiago LimaDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Nitai C HaitDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Aparna MaitiDivision of Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Kumiko KidaDepartment of Gastroenterological Surgery, Yokohama City University School of Medicine, Kanagawa, Japan.
Krista P TerracinaDivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Hiroshi MiyazakiSection of General Internal Medicine, Kojin Hospital, Nagoya, Japan.
Takashi IshikawaDepartment of Breast Surgery, Tokyo Medical University, Tokyo, Japan.
Itaru EndoDepartment of Gastroenterological Surgery, Yokohama City University School of Medicine, Kanagawa, Japan.
Michael R WatersDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Qianya QiDepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Li YanDepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Sheldon MilstienDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Sarah SpiegelDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
Kazuaki TakabeDivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia. kazuaki.takabe@roswellpark.org.
Virginia Commonwealth University · USRoswell Park Comprehensive Cancer Center · USKoujin Hospital · JPTokyo Medical University · JPYokohama City University · JPYokohama City University Medical Center · JP

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
Sphingosine Kinases in Cancer Cell SignalingR01CA061774 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1994 to 2015
$3.8M
Sphingosine-1 Phosphate in Breast Cancer Progression and LymphangiogenesisR01CA160688 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI TAKABE, KAZUAKI · 2012 to 2016
$1.5M
NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA061774NCI NIH HHS R01 CA160688
6 · The paper itself

Abstract

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid mediator, has been implicated in regulation of many processes important for breast cancer progression. Previously, we observed that S1P is exported out of human breast cancer cells by ATP-binding cassette (ABC) transporter ABCC1, but not by ABCB1, both known multidrug resistance proteins that efflux chemotherapeutic agents. However, the pathologic consequences of these events to breast cancer progression and metastasis have not been elucidated. Here, it is demonstrated that high expression of ABCC1, but not ABCB1, is associated with poor prognosis in breast cancer patients. Overexpression of ABCC1, but not ABCB1, in human MCF7 and murine 4T1 breast cancer cells enhanced S1P secretion, proliferation, and migration of breast cancer cells. Implantation of breast cancer cells overexpressing ABCC1, but not ABCB1, into the mammary fat pad markedly enhanced tumor growth, angiogenesis, and lymphangiogenesis with a concomitant increase in lymph node and lung metastases as well as shorter survival of mice. Interestingly, S1P exported via ABCC1 from breast cancer cells upregulated transcription of sphingosine kinase 1 (SPHK1), thus promoting more S1P formation. Finally, patients with breast cancers that express both activated SPHK1 and ABCC1 have significantly shorter disease-free survival. These findings suggest that export of S1P via ABCC1 functions in a malicious feed-forward manner to amplify the S1P axis involved in breast cancer progression and metastasis, which has important implications for prognosis of breast cancer patients and for potential therapeutic targets.

Indexed as

AnimalsATP-Binding Cassette, Sub-Family C ProteinsBreast NeoplasmsFemaleHumansLysophospholipidsMiceMice, Inbred BALB CMice, NudePhosphotransferases (Alcohol Group Acceptor)SphingosineSphingosine KinaseSurvival AnalysisATP-Binding Cassette, Sub-Family C ProteinsLysophospholipidsmultidrug resistance-associated protein 1Phosphotransferases (Alcohol Group Acceptor)Sphingosinesphingosine 1-phosphateSphingosine Kinase

Identifiers

PMID29523764
PMCPMC6071310
OpenAlexW2793775313

What OpenQuestion holds

Textmetadata
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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.