Evidence map›Paper›PMID 39501600›Full record

ArticleCancer medicine2024

The Combined Inhibition of SREBP and mTORC1 Signaling Synergistically Inhibits B-Cell Lymphoma.

Zhenhan Zhu, Wenxia Jiang, Jiehao Zhou, Alexander Robert Maldeney, Jingru Liang, Jing Yang, Wei Luo

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 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
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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

7 authors.

Zhenhan ZhuDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Wenxia JiangDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jiehao ZhouDepartment of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA.
Alexander Robert MaldeneyDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jingru LiangDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jing YangDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Wei LuoDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0003-2826-1723

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
American Cancer SocietyNCI NIH HHS P30 CA082709Ralph W. and Grace M. Showalter Research Trust Fund
6 · The paper itself

Abstract

backgroundThe sterol regulatory element-binding protein (SREBP) pathway is essential for maintaining sterol homeostasis during B cell activation and germinal center B cell proliferation. However, its potential as a therapeutic target to treat B-cell lymphoma remains unclear.

methodsWe examined SREBP protein expression in human B-cell lymphoma samples using immunohistochemistry. Additionally, we conducted in vitro studies using SREBP signaling inhibitors in combination with rapamycin to assess their effects on cell proliferation and lipid metabolism in B-cell lymphoma cells.

resultsOur analysis revealed high levels of SREBP2 protein expression in human B-cell lymphoma samples. Inhibiting SREBP signaling or its downstream target HMG-CoA reductase (HMGCR) with Fatostatin or Simvastatin effectively suppressed B-cell lymphoma cell proliferation. However, B-cell lymphoma cells responded to statin treatment by activating the mTORC1-pS6 pathway, suggesting a compensatory mechanism to overcome statin-induced cell cycle arrest. Combining low-dose statin treatment with the mTOR inhibitor rapamycin produced a synergistic effect, significantly inhibiting B-cell lymphoma proliferation, cell cycle progression, and lipid raft formation.

conclusionsThese results highlight the potential of a combined therapeutic approach targeting both SREBP and mTORC1 as a novel strategy for treating B-cell lymphoma.

Indexed as

Cell ProliferationDrug SynergismLymphoma, B-CellMechanistic Target of Rapamycin Complex 1Signal TransductionSirolimusCell Line, TumorHumansHydroxymethylglutaryl-CoA Reductase InhibitorsPyridinesSimvastatinSterol Regulatory Element Binding Protein 2Sterol Regulatory Element Binding ProteinsThiazolesTOR Serine-Threonine KinasesfatostatinHydroxymethylglutaryl-CoA Reductase InhibitorsMechanistic Target of Rapamycin Complex 1PyridinesSimvastatinSirolimusSREBF2 protein, humanSterol Regulatory Element Binding Protein 2Sterol Regulatory Element Binding ProteinsThiazolesTOR Serine-Threonine Kinases

Identifiers

PMID39501600
PMCPMC11538279

What Socratic holds

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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 Socratic graph.