Evidence map›Paper›PMID 34045496›Full record

ArticleScientific reports2021

Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin.

Michele Lai, Rachele Amato, Veronica La Rocca, Mesut Bilgin, Giulia Freer, Piergiorgio Spezia, Paola Quaranta, Daniele Piomelli, Mauro Pistello

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.6field-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

18 citing papers in PubMed, 28 citations in OpenAlex.

  1. FASEB bioAdvances · 2026
    Article
  2. Article
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  4. Sphingolipid metabolism and regulated cell death in malignant melanoma.Apoptosis : an international journal on programmed cell death · 2024
    Review
  5. Article
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  7. Review
  8. Article
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  10. Article
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  12. Article
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  14. Article
  15. PCSK9 Induces Tissue Factor Expression by Activation of TLR4/NFkB Signaling.International journal of molecular sciences · 2021
    Article
  16. Review
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  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Michele LaiRetrovirus Centre, Department of Translational Medicine and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. michele.lai@unipi.it.
Rachele AmatoInstitute of Life Science, Scuola Sant'Anna Pisa, Pisa, Italy.
Veronica La RoccaInstitute of Life Science, Scuola Sant'Anna Pisa, Pisa, Italy.
Mesut BilginCell Death and Metabolism Unit, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, Copenhagen, Denmark.
Giulia FreerRetrovirus Centre, Department of Translational Medicine and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Piergiorgio SpeziaRetrovirus Centre, Department of Translational Medicine and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Paola QuarantaRetrovirus Centre, Department of Translational Medicine and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Daniele PiomelliAnatomy and Neurobiology, University of California, Irvine, CA, USA.
Mauro PistelloRetrovirus Centre, Department of Translational Medicine and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
University of Pisa · ITScuola Superiore Sant'Anna · ITDanish Cancer Society · DKUniversity of California, Irvine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acid ceramidase (AC) is a lysosomal hydrolase encoded by the ASAH1 gene, which cleaves ceramides into sphingosine and fatty acid. AC is expressed at high levels in most human melanoma cell lines and may confer resistance against chemotherapeutic agents. One such agent, doxorubicin, was shown to increase ceramide levels in melanoma cells. Ceramides contribute to the regulation of autophagy and apoptosis. Here we investigated the impact of AC ablation via CRISPR-Cas9 gene editing on the response of A375 melanoma cells to doxorubicin. We found that doxorubicin activates the autophagic response in wild-type A375 cells, which effectively resist apoptotic cell death. In striking contrast, doxorubicin fails to stimulate autophagy in A375 AC-null cells, which rapidly undergo apoptosis when exposed to the drug. The present work highlights changes that affect melanoma cells during incubation with doxorubicin, in A375 melanoma cells lacking AC. We found that the remarkable reduction in recovery rate after doxorubicin treatment is strictly associated with the impairment of autophagy, that forces the AC-inhibited cells into apoptotic path.

Indexed as

Acid CeramidaseAntineoplastic AgentsApoptosisAutophagyCell Line, TumorCeramidesDoxorubicinHumansMelanomaAcid CeramidaseAntineoplastic AgentsCeramidesDoxorubicin

Identifiers

PMID34045496
PMCPMC8159975
OpenAlexW3165173775

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.