Evidence map›Paper›PMID 38300709›Full record

ArticleThe Journal of clinical investigation2024

The CoREST repressor complex mediates phenotype switching and therapy resistance in melanoma.

Muzhou Wu, Ailish Hanly, Frederick Gibson, Robert Fisher, Samantha Rogers, Kihyun Park, Angelina Zuger, Kevin Kuang, Jay H Kalin, Sarah Nocco and 8 more

Open access · goldAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

14 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Role of Galectin-1 in the Pathogenesis of Melanoma.Journal of cancer science and clinical therapeutics · 2025
    Article
  12. SpecificbioRxiv : the preprint server for biology · 2024
    Article
  13. Article
  14. Review
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

18 authors at 2 institutions in 1 country.

Muzhou WuDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Ailish HanlyDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Frederick GibsonDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Robert FisherDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Samantha RogersDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Kihyun ParkDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Angelina ZugerDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Kevin KuangDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Jay H KalinDivision of Genetics, Departments of Medicine and Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Sarah NoccoDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Matthew ColeDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Amy XiaoDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Filisia AgusBioinformatics Program, Boston University, Boston, Massachusetts, USA.
Adam LabadorfBioinformatics Program, Boston University, Boston, Massachusetts, USA.
Samuel BeckDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Marianne CollardDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Philip A ColeDivision of Genetics, Departments of Medicine and Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Rhoda M AlaniDepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
Boston University · USBrigham and Women's Hospital · US

Funding

Protein Acylation and Methylation Mechanisms_Administrative SupplementR37GM062437 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A · 2013 to 2022
$4.1M
NIGMS NIH HHS R37 GM062437
6 · The paper itself

Abstract

Virtually all patients with BRAF-mutant melanoma develop resistance to MAPK inhibitors largely through nonmutational events. Although the epigenetic landscape is shown to be altered in therapy-resistant melanomas and other cancers, a specific targetable epigenetic mechanism has not been validated. Here, we evaluated the corepressor for element 1-silencing transcription factor (CoREST) epigenetic repressor complex and the recently developed bivalent inhibitor corin within the context of melanoma phenotype plasticity and therapeutic resistance. We found that CoREST was a critical mediator of the major distinct melanoma phenotypes and that corin treatment of melanoma cells led to phenotype reprogramming. Global assessment of transcript and chromatin changes conferred by corin revealed specific effects on histone marks connected to epithelial-mesenchymal transition-associated (EMT-associated) transcription factors and the dual-specificity phosphatases (DUSPs). Remarkably, treatment of BRAF inhibitor-resistant (BRAFi-R) melanomas with corin promoted resensitization to BRAFi therapy. DUSP1 was consistently downregulated in BRAFi-R melanomas, which was reversed by corin treatment and associated with inhibition of p38 MAPK activity and resensitization to BRAFi therapies. Moreover, this activity was recapitulated by the p38 MAPK inhibitor BIRB 796. These findings identify the CoREST repressor complex as a central mediator of melanoma phenotype plasticity and resistance to targeted therapy and suggest that CoREST inhibitors may prove beneficial for patients with BRAFi-resistant melanoma.

Indexed as

MelanomaCell Line, TumorCo-Repressor ProteinsDrug Resistance, NeoplasmHumansp38 Mitogen-Activated Protein KinasesPhenotypeProtein Kinase InhibitorsProto-Oncogene Proteins B-rafCo-Repressor Proteinsp38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafDermatologyDrug therapyEpigeneticsMelanomaOncology

Identifiers

PMID38300709
PMCPMC10940100
OpenAlexW4391450925

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.