Evidence map›Paper›PMID 28785021›Full record

ArticleScientific reports2017

Complete Acid Ceramidase ablation prevents cancer-initiating cell formation in melanoma cells.

Michele Lai, Natalia Realini, Marco La Ferla, Ilaria Passalacqua, Giulia Matteoli, Anand Ganesan, Mauro Pistello, Chiara Maria Mazzanti, Daniele Piomelli

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

44 citing papers in PubMed, 64 citations in OpenAlex.

  1. Review
  2. FASEB bioAdvances · 2026
    Article
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  8. Drug Resistance: The Role of Sphingolipid Metabolism.International journal of molecular sciences · 2025
    Review
  9. Cardiac dysfunction and altered gene expression in acid ceramidase-deficient mice.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  10. Regulation of autophagy by non-coding RNAs in human glioblastoma.Medical oncology (Northwood, London, England) · 2024
    Review
  11. 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

9 authors at 4 institutions in 2 countries.

Michele LaiDrug Discovery and Development, Istituto Italiano di Tecnologia, Genova, 16163, Italy.
Natalia RealiniDrug Discovery and Development, Istituto Italiano di Tecnologia, Genova, 16163, Italy.
Marco La FerlaPisa Science Foundation, Pisa, 56121, Italy.
Ilaria PassalacquaRetrovirus Center and Virology Section, Department of Translational Research, University of Pisa, Pisa, Italy.
Giulia MatteoliRetrovirus Center and Virology Section, Department of Translational Research, University of Pisa, Pisa, Italy.
Anand GanesanDepartment of Dermatology, University of California, Irvine, California, 92868, USA.
Mauro PistelloRetrovirus Center and Virology Section, Department of Translational Research, University of Pisa, Pisa, Italy.
Chiara Maria MazzantiPisa Science Foundation, Pisa, 56121, Italy. c.mazzanti@fpscience.it.
Daniele PiomelliDepartments of Anatomy and Neurobiology, Pharmacology and Biological Chemistry, University of California, Irvine, CA, 92617, USA. piomelli@uci.edu.
University of California, Irvine · USUniversity of Pisa · ITFondazione Pisa · ITItalian Institute of Technology · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acid ceramidase (AC) is a lysosomal cysteine hydrolase that catalyzes the conversion of ceramide into fatty acid and sphingosine. This reaction lowers intracellular ceramide levels and concomitantly generates sphingosine used for sphingosine-1-phosphate (S1P) production. Since increases in ceramide and consequent decreases of S1P reduce proliferation of various cancers, AC might offer a new target for anti-tumor therapy. Here we used CrispR-Cas9-mediated gene editing to delete the gene encoding for AC, ASAH1, in human A375 melanoma cells. ASAH1-null clones show significantly greater accumulation of long-chain saturated ceramides that are substrate for AC. As seen with administration of exogenous ceramide, AC ablation blocks cell cycle progression and accelerates senescence. Importantly, ASAH1-null cells also lose the ability to form cancer-initiating cells and to undergo self-renewal, which is suggestive of a key role for AC in maintaining malignancy and self-renewal of invasive melanoma cells. The results suggest that AC inhibitors might find therapeutic use as adjuvant therapy for advanced melanoma.

Indexed as

Cell ProliferationCellular SenescenceGene Knockout TechniquesAcid CeramidaseCell Line, TumorCeramidesClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9HumansLysophospholipidsMelanocytesSphingosineAcid CeramidaseASAH1 protein, humanCeramidesCRISPR-Associated Protein 9LysophospholipidsSphingosinesphingosine 1-phosphate

Identifiers

PMID28785021
PMCPMC5547127
OpenAlexW2741769501

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Registered trials

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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.