Evidence map›Paper›PMID 33026191›Full record

ArticleEMBO molecular medicine2020

LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma.

Lukas Leiendecker, Pauline S Jung, Izabela Krecioch, Tobias Neumann, Alexander Schleiffer, Karl Mechtler, Thomas Wiesner, Anna C Obenauf

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.5field-weighted citation impact, top 5% 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

45 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Review
  3. Pharmacologic reversion of Merkel cell carcinoma via CBP/p300 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Epigenetic repression ofiScience · 2024
    Article
  18. Review
  19. Article
  20. bioRxiv : the preprint server for biology · 2023
    Article
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 at 3 institutions in 1 country.

Lukas Leiendecker *Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0002-6164-3953
Pauline S Jung *Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0002-8864-4091
Izabela KreciochResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0002-3629-8123
Tobias NeumannResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0003-3908-4224
Alexander SchleifferResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0001-6251-2747
Karl MechtlerInstitute of Molecular Biotechnology (IMBA), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0002-3392-9946
Thomas WiesnerDepartment of Dermatology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-5877-2992
Anna C ObenaufResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.ORCID 0000-0002-9556-5914
Research Institute of Molecular Pathology · ATInstitute of Molecular Biotechnology · ATMedical University of Vienna · AT

Funding

European Research Council (ERC) ERC-StG-759590Vienna Science and Technology Fund (WWTF) #LS16-063
6 · The paper itself

Abstract

Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that lacks actionable mutations, which could be utilized for targeted therapies. Epigenetic regulators governing cell identity may represent unexplored therapeutic entry points. Here, we targeted epigenetic regulators in a pharmacological screen and discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. We show that LSD1 inhibition in MCC disrupts the LSD1-CoREST complex leading to displacement and degradation of HMG20B (BRAF35), a poorly characterized complex member that is essential for MCC proliferation. Inhibition of LSD1 causes derepression of transcriptional master regulators of the neuronal lineage, activates a gene expression signature resembling normal Merkel cells, and induces cell cycle arrest and cell death. Our study unveils the importance of LSD1 for maintaining cellular plasticity and proliferation in MCC. There is also growing evidence that cancer cells exploit cellular plasticity and dedifferentiation programs to evade destruction by the immune system. The combination of LSD1 inhibitors with checkpoint inhibitors may thus represent a promising treatment strategy for MCC patients.

Indexed as

Carcinoma, Merkel CellSkin NeoplasmsCell DeathCell DifferentiationHistone DemethylasesHumansHistone DemethylasesKDM1A protein, humanepigeneticsHMG20BLSD1merkel cell carcinomatargeted therapy

Identifiers

PMID33026191
PMCPMC7645387
OpenAlexW3092541748

What Socratic 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 Socratic graph.