Evidence map›Paper›PMID 37676710›Full record

ArticleCancer discovery2023

Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer.

Sandra Santasusagna, Shijia Zhu, Vijayakumar Jawalagatti, Marc Carceles-Cordon, Adam Ertel, Saioa Garcia-Longarte, Won-Min Song, Naoto Fujiwara, Peiyao Li, Isabel Mendizabal and 15 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.4field-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

15 citing papers in PubMed, 17 citations in OpenAlex.

  1. SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  2. Review
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  8. METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  9. Article
  10. [The study on effect of EIF3B in laryngeal carcinoma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025
    Article
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  12. 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

25 authors at 8 institutions in 2 countries.

Sandra Santasusagna *Department of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0002-4919-4577
Shijia Zhu *Department of Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.ORCID 0000-0002-2368-2361
Vijayakumar Jawalagatti *Department of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0001-8492-5550
Marc Carceles-CordonDepartment of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0009-0004-1082-0587
Adam ErtelDepartment of Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0001-7455-1559
Saioa Garcia-LongarteCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain.ORCID 0000-0001-5412-4234
Won-Min SongDepartment of Genetics and Genome Sciences, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York.ORCID 0000-0003-0948-119X
Naoto FujiwaraDepartment of Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.ORCID 0000-0002-4109-3421
Peiyao LiDepartment of Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0001-9119-2498
Isabel MendizabalCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain.ORCID 0000-0002-9018-3474
Daniel P PetrylakDepartment of Oncology, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.ORCID 0000-0001-6165-5797
William Kevin KellyDepartment of Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0003-2629-672X
E Premkumar ReddyDepartment of Oncological Sciences, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York.ORCID 0000-0002-0667-4191
Liguo WangDepartment of Biochemistry and Molecular Biology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0003-2072-4826
Matthew J SchiewerDepartment of Pharmacology, Physio-logy, and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0002-2325-4228
Amaia LujambioDepartment of Oncological Sciences, Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York.ORCID 0000-0002-2798-1481
Jeffrey KarnesDepartment of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0003-2339-5925
Karen E KnudsenDepartment of Pharmacology, Physio-logy, and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0002-1301-890X
Carlos Cordon-CardoDepartment of Pathology. Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York.ORCID 0000-0003-0858-5624
Haidong DongDepartment of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0002-5782-2983
Haojie HuangDepartment of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0003-2751-6413
Arkaitz CarracedoCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Spain.ORCID 0000-0001-5957-1260
Yujin HoshidaDepartment of Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.ORCID 0000-0001-9430-1426
Veronica Rodriguez-BravoDepartment of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0002-7363-3672
Josep Domingo-DomenechDepartment of Urology, Mayo Comprehensive Cancer Center, Rochester, Minnesota.ORCID 0000-0002-7870-7511
Mayo Clinic · USSidney Kimmel Cancer Center · USTisch Hospital · USCIC bioGUNE · ESThe University of Texas Southwestern Medical Center · USIkerbasque · ESUniversity of Minnesota · USYale Cancer Center · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Reverse-engineering precision liver cancer chemopreventionR01CA233794 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HOSHIDA, YUJIN · 2019 to 2023
$3.5M
Molecular Prognostic Indicators in Liver Cirrhosis and CancerR01DK099558 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HOSHIDA, YUJIN · 2013 to 2016
$2.6M
Determine the Microphthalmia Transcription Factor (MITF)-regulated cell rewiring mechanisms in lethal prostate cancerR01CA261925 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Josep Maria Domingo-Domenech · 2021 to 2026
$2.2M
Role of Nuclear Pore-Regulated Mechanisms in Prostate Cancer AggressivenessR01CA237398 · NCI · THOMAS JEFFERSON UNIVERSITY · PI RODRIGUEZ-BRAVO, VERONICA · 2020 to 2024
$2.0M
Mechanisms and therapeutic targeting of lethal prostate cancer master regulator transcription factorsR01CA280999 · NCI · MAYO CLINIC ROCHESTER · PI Josep Maria Domingo-Domenech, Veronica Rodriguez-Bravo · 2024 to 2026
$1.6M
NCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA233794NCI NIH HHS R01 CA237398NCI NIH HHS R01 CA261925NCI NIH HHS R01 CA280999NIDDK NIH HHS R01 DK099558
6 · The paper itself

Abstract

Signaling rewiring allows tumors to survive therapy. Here we show that the decrease of the master regulator microphthalmia transcription factor (MITF) in lethal prostate cancer unleashes eukaryotic initiation factor 3B (eIF3B)-dependent translation reprogramming of key mRNAs conferring resistance to androgen deprivation therapy (ADT) and promoting immune evasion. Mechanistically, MITF represses through direct promoter binding eIF3B, which in turn regulates the translation of specific mRNAs. Genome-wide eIF3B enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) showed specialized binding to a UC-rich motif present in subsets of 5' untranslated regions. Indeed, translation of the androgen receptor and major histocompatibility complex I (MHC-I) through this motif is sensitive to eIF3B amount. Notably, pharmacologic targeting of eIF3B-dependent translation in preclinical models sensitizes prostate cancer to ADT and anti-PD-1 therapy. These findings uncover a hidden connection between transcriptional and translational rewiring promoting therapy-refractory lethal prostate cancer and provide a druggable mechanism that may transcend into effective combined therapeutic strategies. SIGNIFICANCE: Our study shows that specialized eIF3B-dependent translation of specific mRNAs released upon downregulation of the master transcription factor MITF confers castration resistance and immune evasion in lethal prostate cancer. Pharmacologic targeting of this mechanism delays castration resistance and increases immune-checkpoint efficacy. This article is featured in Selected Articles from This Issue, p. 2489.

Indexed as

Prostatic NeoplasmsProstatic Neoplasms, Castration-ResistantAndrogen AntagonistsCastrationHumansImmune EvasionMaleReceptors, AndrogenTranscription FactorsAndrogen AntagonistsReceptors, AndrogenTranscription Factors

Identifiers

PMID37676710
PMCPMC10714140
OpenAlexW4386495980

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.