Evidence map›Paper›PMID 41405996›Full record

ArticleCell reports2025

A BRN2:MYC transcriptional axis regulates interconversion between therapy-resistant and tumorigenic phenotypes in melanoma.

Yuntian Zhang, Marcus A Urquijo, Rebecca G Zitnay, Kayla Marks, Rachel L Belote, Maike M K Hansen, Montana Ferita, Hannah M Neuendorf, Tong Liu, Eric A Smith and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. MYC as a key target for melanoma therapy.Frontiers in cell and developmental biology · 2026
    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

34 authors.

Yuntian ZhangHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Marcus A UrquijoHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT 84103, USA.
Rebecca G ZitnayHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210, USA; Department of Chemical Engineering, University of Utah, Salt Lake City, UT 84103, USA.
Kayla MarksHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Rachel L BeloteHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210, USA.
Maike M K HansenRadboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands.
Montana FeritaDepartment of Mathematics, University of Utah, Salt Lake City, UT, USA.
Hannah M NeuendorfCancer Drug Mechanisms Group, Cancer Research Department, QIMR Berghofer, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4059, Australia.
Tong LiuHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Eric A SmithDepartment of Pathology, University of Utah, Salt Lake City, UT 84132, USA.
Elnaz Mirzaei MehrabadHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Miroslav HejnaDepartment of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Tarek E MoustafaDepartment of Chemical Engineering, University of Utah, Salt Lake City, UT 84103, USA.
Devin LangeSCI Institute and Kahlert School of Computing, University of Utah, Salt Lake City, UT 84112, USA.
Min HuHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT 84103, USA.
Fatemeh Vand-RajabpourDepartment of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Anne DoneHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Carly A BeckerHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Matthew LiebermanHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA.
Matthew ChangDepartment of Dermatology, Oregon Health and Science University, Portland, OR 97239, USA; Departments of Biomedical Engineering and Oncological Sciences, Oregon Health and Science University, Portland, OR 97239, USA; Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA; Operative Care Division, VA Portland Health Care System, Portland, OR 97239, USA.
Brian K LohmanHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Chris J StubbenHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Melissa Q ReevesHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA.
Xiaoyang ZhangHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT 84103, USA.
Leor S WeinbergerGladstone Center for Cell Circuitry, Gladstone Institutes, San Francisco, CA 94158, USA; Departments of Pharmaceutical Chemistry and Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Matthew W VanBrocklinHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Dekker C DeaconHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Douglas GrossmanHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Benjamin T SpikeHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT 84103, USA.
Alexander LexHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; SCI Institute and Kahlert School of Computing, University of Utah, Salt Lake City, UT 84112, USA.
Glen M BoyleCancer Drug Mechanisms Group, Cancer Research Department, QIMR Berghofer, Brisbane, QLD 4006, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4059, Australia; School of Biomedical Science, Faculty of Health, Medicine and Behavioral Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
Rajan KulkarniDepartment of Dermatology, Oregon Health and Science University, Portland, OR 97239, USA; Departments of Biomedical Engineering and Oncological Sciences, Oregon Health and Science University, Portland, OR 97239, USA; Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA; Operative Care Division, VA Portland Health Care System, Portland, OR 97239, USA.
Thomas A ZangleHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Chemical Engineering, University of Utah, Salt Lake City, UT 84103, USA.
Robert L Judson-TorresHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA; Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT 84103, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. Electronic address: robert.judson-torres@hci.utah.edu.

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
MicroRNA-Based Detection of Barriers to Melanoma ProgressionDP5OD019787 · OD · UNIVERSITY OF UTAH · PI JUDSON-TORRES, ROBERT LAIRD · 2014 to 2018
$1.9M
Nevus associated microRNAs as mediators of BRAF-induced growth arrest and biomarkers of melanoma progressionR01CA229896 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI JUDSON-TORRES, ROBERT LAIRD · 2021 to 2025
$1.8M
Development and Pre-Clinical Validation of Quantitative Imaging of Cell State Kinetics (QuICK) for Functional Precision OncologyR01CA276653 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Robert Laird Judson-Torres, Thomas Andrew Zangle · 2023 to 2026
$1.6M
NCI NIH HHS P30 CA042014NCI NIH HHS R01 CA229896NCI NIH HHS R01 CA276653NIH HHS DP5 OD019787
6 · The paper itself

Abstract

Metastatic spread and therapeutic resistance are the principal causes of cancer mortality. For melanoma, these processes rely on the capacity of cells to switch between transcriptional states. Although targeting transcriptional states pharmacologically is promising, the mechanisms by which melanoma cells switch between states-and how these processes differ from melanocytes-remain poorly understood. Here, we isolate distinct melanoma states with unique phenotypes: a MYC-driven state, essential for tumor initiation yet sensitive to BRAF inhibition, and a dedifferentiated, invasive BRN2-high state enriched in therapy-resistant cells but not directly tumorigenic. Transitions between phenotypes occur through intermediate, more differentiated states. Unexpectedly, the BRN2-high state is also present in melanocytes, whereas the MYC state is exclusive to melanoma. Melanoma cells also exhibit an increased frequency of transitions across states. These findings highlight that accelerated phenotypic switching, rather than mere state diversity, is a defining feature of melanoma progression.

Indexed as

CarcinogenesisDrug Resistance, NeoplasmHomeodomain ProteinsMelanomaPOU Domain FactorsProto-Oncogene Proteins c-mycTranscription, GeneticAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMelanocytesMicePhenotypeProto-Oncogene Proteins B-rafHomeodomain ProteinsPOU Domain FactorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-myctranscription factor Brn-2BRN2CP: CancermelanocytesmelanomaMITFMYConcogenic competencephenotype switchingplasticityquantitative phase imagingsingle-cell sequencing

Identifiers

PMID41405996
PMCPMC12834598

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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.