Evidence mapPaperPMID 39580596Full record

ArticleCell death and differentiation2025

UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer.

Le Zhang, Prashanthi Ramesh, Lidia Atencia Taboada, Rebecca Roessler, Dick W Zijlmans, Michiel Vermeulen, Daisy I Picavet-Havik, Nicole N van der Wel, Frédéric M Vaz, Jan Paul Medema

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In one paragraph

Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
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  3. pH-responsive magnetic FeMaterials today. Bio · 2025
    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

10 authors.

Le ZhangLEXOR, Center for Experimental Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Prashanthi RameshLEXOR, Center for Experimental Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Lidia Atencia TaboadaLEXOR, Center for Experimental Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Rebecca RoesslerLEXOR, Center for Experimental Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Dick W ZijlmansDepartment of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.
Michiel VermeulenDepartment of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-0836-6894
Daisy I Picavet-HavikMedical Biology - MB Core Facility, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Nicole N van der WelMedical Biology - MB Core Facility, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Frédéric M VazAmsterdam UMC location University of Amsterdam, Department of Laboratory Medicine and Pediatrics, Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-9048-1041
Jan Paul MedemaLEXOR, Center for Experimental Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. j.p.medema@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-3045-2924

Funding

KWF Kankerbestrijding (Dutch Cancer Society) 14374
6 · The paper itself

Abstract

Elevated de novo lipid synthesis is a remarkable adaptation of cancer cells that can be exploited for therapy. However, the role of altered lipid metabolism in the regulation of apoptosis is still poorly understood. Using thermal proteome profiling, we identified Manidipine-2HCl, targeting UGT8, a key enzyme in the synthesis of sulfatides. In agreement, lipidomic analysis indicated that sulfatides are strongly reduced in colorectal cancer cells upon treatment with Manidipine-2HCl. Intriguingly, this reduction led to severe mitochondrial swelling and a strong synergism with BH3 mimetics targeting BCL-XL, leading to the activation of mitochondria-dependent apoptosis. Mechanistically, Manidipine-2HCl enhanced mitochondrial BAX localization in a sulfatide-dependent fashion, facilitating its activation by BH3 mimetics. In conclusion, our data indicates that UGT8 mediated synthesis of sulfatides controls mitochondrial homeostasis and BAX localization, dictating apoptosis sensitivity of colorectal cancer cells.

Indexed as

Apoptosisbcl-2-Associated X ProteinColorectal NeoplasmsSulfoglycosphingolipidsCell Line, TumorHumansMitochondriaBAX protein, humanbcl-2-Associated X ProteinSulfoglycosphingolipids

Identifiers

PMID39580596
PMCPMC11982410

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.