Evidence map›Paper›PMID 39328328›Full record

ArticleWorld journal of oncology2024

Targeting SNAI1-Mediated Colorectal Cancer Chemoresistance and Stemness by Sphingosine Kinase 2 Inhibition.

Harinarayanan Janakiraman, Zachary Gao, Yun Zhu, Jiangling Dong, Scott A Becker, Alhaji Janneh, Besim Ogretmen, E Ramsay Camp

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in World journal of oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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

8 authors.

Harinarayanan JanakiramanMichael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Zachary GaoMichael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Yun ZhuMD Anderson Cancer Center, Houston, TX 77030, USA.
Jiangling DongMichael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Scott A BeckerMolecular and Systems Pharmacology, Emory University, Atlanta, GA 30322, USA.
Alhaji JannehDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Besim OgretmenDepartment of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
E Ramsay CampMichael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.ORCID https://orcid.org/0000-0003-0005-7536

Funding

Project 3: Targeting SK2/S1P Signaling for the Regulation of c-Myc and Tumor SuppressionP01CA203628 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2016 to 2021
$8.9M
Ceramide Signaling in the Regulation of Head & Neck Cancer Cell Death and TherapyR01DE016572 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2005 to 2025
$7.4M
Research Supplement to Promote Diversity in Health-Related ResearchR01CA214461 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Besim Ogretmen · 2018 to 2026
$3.3M
Sphingolipid Metabolism and Signaling in the Regulation of Senescence and AgingR56AG069769 · NIA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2020 to 2020
$370k
CSRD VA I01 CX001880NCI NIH HHS P01 CA203628NCI NIH HHS R01 CA214461NIA NIH HHS R56 AG069769NIDCR NIH HHS R01 DE016572
6 · The paper itself

Abstract

Background: Epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs), and colorectal cancer (CRC) therapy resistance are closely associated. Prior reports have demonstrated that sphingosine-1-phosphate (S1P) supports stem cells and maintains the CSC phenotype. We hypothesized that the EMT inducer SNAI1 drives S1P signaling to amplify CSC self-renewal capacity and chemoresistance. Methods: CRC cell lines with or without ectopic expression of SNAI1 were used to study the role of S1P signaling as mediators of cancer stemness and 5-fluorouracil (5FU) chemoresistance. The therapeutic ability of sphingosine kinase 2 (SPHK2) was assessed using siRNA and ABC294640, a SPHK2 inhibitor. CSCs were isolated from patient-derived xenografts (PDXs) and assessed for SPHK2 and SNAI1 expression. Results: Ectopic SNAI1 expressing cell lines demonstrated elevated SPHK2 expression and increased SPHK2 promoter activity. SPHK2 inhibition with siRNA or ABC294640 ablated Conclusions: SNAI1/SPHK2 signaling mediates cancer stemness and 5FU resistance, implicating S1P as a therapeutic target for CRC. The S1P inhibitor ABC294640 holds potential as a therapeutic agent to target CSCs in therapy refractory CRC.

Indexed as

Cancer stem cellsChemotherapy resistanceColorectal cancerEpithelial-to-mesenchymal transitionSphingosine

Identifiers

PMID39328328
PMCPMC11424120

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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.