Evidence map›Paper›PMID 37460872›Full record

ArticleNature cancer2023

The Akt/mTOR and MNK/eIF4E pathways rewire the prostate cancer translatome to secrete HGF, SPP1 and BGN and recruit suppressive myeloid cells.

Daniela Brina, Adele Ponzoni, Martina Troiani, Bianca Calì, Emiliano Pasquini, Giuseppe Attanasio, Simone Mosole, Michela Mirenda, Mariantonietta D'Ambrosio, Manuel Colucci and 29 more

Open access · greenAbstract read
In one paragraph

Article in Nature cancer, 2023. 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
10.0field-weighted citation impact, top 1% 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, 61 citations in OpenAlex.

  1. Article
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  9. Colorectal Cancer Cell's Weapon: RNF32 Engages SPP1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  11. American journal of cancer research · 2026
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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

39 authors at 15 institutions in 5 countries.

Daniela BrinaInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Adele PonzoniInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Martina TroianiInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Bianca CalìInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Emiliano PasquiniInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Giuseppe AttanasioInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Simone MosoleInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Michela MirendaInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Mariantonietta D'AmbrosioInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Manuel ColucciInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Ilaria GucciniInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Ajinkya RevandkarInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Abdullah AlajatiInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Toma TebaldiYale Cancer Center and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-0625-1631
Deborah DonzelInstitute of Biophysics, CNR Unit at Trento, Povo, Italy.
Fabio LauriaInstitute of Biophysics, CNR Unit at Trento, Povo, Italy.
Nahjme ParhizgariInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Aurora ValdataInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Martino MaddalenaInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Arianna CalcinottoInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.ORCID 0000-0003-1746-6424
Marco BolisFaculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.ORCID 0000-0003-4377-5079
Andrea RinaldiInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Simon BarryIMED Oncology AstraZeneca, Li Ka Shing Centre, Cambridge, UK.ORCID 0000-0002-8511-0588
Jan Hendrik RüschoffDepartment of Pathology and Molecular Pathology, University Hospital Zurich (USZ), Zurich, Switzerland.
Marianna SabbadinVeneto Institute of Oncology, IOV-IRCCS, Padua, Italy.
Semini SumanasuriyaInstitute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
Mateus CrespoInstitute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
Adam SharpInstitute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
Wei YuanInstitute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
Mathew GrinuCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Alexandra BoyleCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Cynthia MillerCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Lloyd TrotmanCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.ORCID 0000-0002-4794-1559
Nicolas Delaleu2cSysBioMed, TI, Contra, Switzerland.
Matteo FassanVeneto Institute of Oncology, IOV-IRCCS, Padua, Italy.
Holger MochDepartment of Pathology and Molecular Pathology, University Hospital Zurich (USZ), Zurich, Switzerland.ORCID 0000-0002-7986-2839
Gabriella VieroInstitute of Biophysics, CNR Unit at Trento, Povo, Italy.ORCID 0000-0002-6755-285X
Johann de BonoInstitute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.ORCID 0000-0002-2034-595X
Andrea AlimontiInstitute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. andrea.alimonti@ior.usi.ch.ORCID 0000-0002-9362-2313
Institute of Oncology Research · CHRoyal Marsden NHS Foundation Trust · GBCold Spring Harbor Laboratory · USUniversity Hospital of Zurich · CH490 BioTech (United States) · USAstraZeneca (United Kingdom) · GBBiocon (Switzerland) · CHBoard of the Swiss Federal Institutes of Technology · CHETH Zurich · CHHarvard University · USIstituto Oncologico Veneto · ITSIB Swiss Institute of Bioinformatics · CHUniversity Hospital Bonn · DEUniversity of Padua · ITYale Cancer Center · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
Metastasis of PTEN Mutant Prostate CancerR01CA275128 · NCI · COLD SPRING HARBOR LABORATORY · PI TROTMAN, LLOYD C · 2022 to 2025
$2.7M
Medical Research Council MR/W018217/1NCI NIH HHS P30 CA045508NCI NIH HHS R01 CA275128
6 · The paper itself

Abstract

Cancer is highly infiltrated by myeloid-derived suppressor cells (MDSCs). Currently available immunotherapies do not completely eradicate MDSCs. Through a genome-wide analysis of the translatome of prostate cancers driven by different genetic alterations, we demonstrate that prostate cancer rewires its secretome at the translational level to recruit MDSCs. Among different secreted proteins released by prostate tumor cells, we identified Hgf, Spp1 and Bgn as the key factors that regulate MDSC migration. Mechanistically, we found that the coordinated loss of Pdcd4 and activation of the MNK/eIF4E pathways regulate the mRNAs translation of Hgf, Spp1 and Bgn. MDSC infiltration and tumor growth were dampened in prostate cancer treated with the MNK1/2 inhibitor eFT508 and/or the AKT inhibitor ipatasertib, either alone or in combination with a clinically available MDSC-targeting immunotherapy. This work provides a therapeutic strategy that combines translation inhibition with available immunotherapies to restore immune surveillance in prostate cancer.

Indexed as

Prostatic NeoplasmsProtein Serine-Threonine KinasesBiglycanEukaryotic Initiation Factor-4EHepatocyte Growth FactorHumansMaleMyeloid CellsOsteopontinPhosphorylationProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesBGN protein, humanBiglycanEukaryotic Initiation Factor-4EHepatocyte Growth FactorHGF protein, humanOsteopontinProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktSPP1 protein, humanTOR Serine-Threonine Kinases

Identifiers

PMID37460872
PMCPMC11331482
OpenAlexW4384522527

What OpenQuestion holds

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Registered trials

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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.