Evidence map›Paper›PMID 40513567›Full record

ArticleMolecular cell2025

The immortality mechanism of TERT promoter mutant cancers is self-reinforcing and reversible.

Nicholas O Stevers, Somang Kim, Jimmy Bo Yuan, Carter J Barger, Chibo Hong, Olivia Lenzo, Andrew M McKinney, Samuel H Wu, Yu Jin Lee, Darwin W Kwok and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 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. Article
  3. Extracellular vesicles for delivery of functional telomerase.Cell communication and signaling : CCS · 2025
    Article
  4. 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

16 authors.

Nicholas O SteversDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Somang KimDepartment of Physics, University of Illinois, Urbana-Champaign, Champaign, IL, USA; Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Champaign, IL, USA; Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Champaign, IL, USA.
Jimmy Bo YuanDepartment of Physics, University of Illinois, Urbana-Champaign, Champaign, IL, USA; Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Champaign, IL, USA; Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Champaign, IL, USA.
Carter J BargerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Chibo HongDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Olivia LenzoDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Andrew M McKinneyDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Samuel H WuDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Yu Jin LeeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Darwin W KwokDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Abigail K SuwalaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Christina L AppinDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
John D GordanQuantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA, USA.
Annette M MolinaroDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Jun S SongDepartment of Physics, University of Illinois, Urbana-Champaign, Champaign, IL, USA; Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Champaign, IL, USA; Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Champaign, IL, USA. Electronic address: songj@illinois.edu.
Joseph F CostelloDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. Electronic address: joseph.costello@ucsf.edu.

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Project 4: Multi-modality Metabolic Imaging for Monitoring Molecular Sub-types of GliomaP01CA118816 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Susan M Chang, Janine Marie Lupo · 2007 to 2026
$44.7M
Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
Predicting Transcriptional and Epigenetic Networks in Cancer from Sequencing DataR01CA163336 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Jun S Song · 2012 to 2026
$4.4M
Development of Technologies for Efficient In Vivo Prime EditingR01GM141296 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI PEREZ-PINERA, PABLO, SONG, JUN S · 2021 to 2024
$2.1M
The Immortality and Evolution of Adult Brain TumorsR50CA274229 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Chibo Hong · 2022 to 2026
$899k
FOXM1-RHNO1 Oncogenic Axis in Ovarian CancerK00CA212470 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BARGER, CARTER J · 2018 to 2020
$245k
Identification of a GABP Feedback Loop and its Role in Tumor Cell ImmortalityF31CA254067 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVERS, NICHOLAS OLIVER · 2020 to 2022
$125k
Signaling Regulation of GABP-Mediated Mutant TERT Promoter Activation in GliomaF31CA243187 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCKINNEY, ANDREW · 2019 to 2020
$80k
NCI NIH HHS F31 CA243187NCI NIH HHS F31 CA254067NCI NIH HHS K00 CA212470NCI NIH HHS P01 CA118816NCI NIH HHS P30 CA082103NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA163336NCI NIH HHS R50 CA274229NCI NIH HHS T32 CA151022NIGMS NIH HHS R01 GM141296
6 · The paper itself

Abstract

Activating mutations in the telomerase reverse transcriptase (TERT) promoter are prevalent in cancer and enable limitless cell division characteristic of immortal cells. Solving the immortality mechanism represents a major step toward selective reversal in cancer cells. TERT promoter (TERTp) mutations create a de novo E26 transformation-specific (ETS) transcription factor binding motif. Here, we analyzed 53 cell lines representing 16 cancer types and 6 recurrent TERTp mutations and found that the GA-binding protein (GABP) tetramer is responsible for promoter activation in all cases. Surprisingly, TERT expression is maintained after tetramer depletion. Further investigation revealed an underlying network of auto-suppression among the GABP subunits. Release from it drives TERT maintenance via upregulated GABP dimers or a paralogous tetramer. The GABPB1L tetramer is therefore a pan-cancer, pan-mutation activator of the mutant TERT promoter, but it is replaceable. Domains shared by the three GABP complexes, rather than solely the B1L tetramer, are mutation-specific vulnerabilities.

Indexed as

Cell Transformation, NeoplasticGA-Binding Protein Transcription FactorMutationNeoplasmsPromoter Regions, GeneticTelomeraseBinding SitesCell Line, TumorGene Expression Regulation, NeoplasticHumansProtein MultimerizationGA-Binding Protein Transcription FactorGABPB1 protein, humanTelomeraseTERT protein, humanGABPnoncoding mutationpan-cancertelomereTERT promoter mutationtumor immortality

Identifiers

PMID40513567
PMCPMC12302846

What Socratic holds

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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.