ArticleNature2017
mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 145 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% of its field
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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.
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Who cites it
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- Genetic variants in RUNX3, AMD1 and MSRA in the methionine metabolic pathway and survival in nonsmall cell lung cancer patients.International journal of cancer · 2019Pooled it
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- A Neurotensin Brake on Exploratory Drive under Persistent Threat.bioRxiv : the preprint server for biology · 2026Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- NNMT Loss Drives Cancer Progression by enhancing SAM availability for mTORC1 Signaling and Chromatin Methylation.bioRxiv : the preprint server for biology · 2026Article
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- Dysregulation of the urea cycle - potential targets for treatment and diagnosis in prostate cancer.Expert reviews in molecular medicine · 2026Review
- Review
- Hypusination of the translation factor eIF5A regulates mitochondrial tRNA processing to promote prostate cancer aggressiveness.Nature communications · 2026Article
- Androgen Receptor Drives Polyamine Synthesis, Creating a Vulnerability for Prostate Cancer.Cancer research · 2026Article
- Article
- ODC1 Polyamine Metabolism Drives Prostate Cancer via AKT and Splicing.Journal of cellular and molecular medicine · 2026Article
- The polyamine inhibitor SAM486A increases the efficacy of adagrasib in non-small cell lung cancer cells harboring KRASBiological research · 2026Article
- Using animal models to decipher the role of polyamines in the pancreas and β Cell.Amino acids · 2026Review
- Polyamines in Cancer: Mechanisms, Metabolic Targets, and Therapeutic Opportunities.Anti-cancer agents in medicinal chemistry · 2026Review
- Article
- Cancer Cell-Secreted miR-33a Reduces Stress Granule Formation by Targeting Polyamine Metabolism in Stroma to Promote Tumourigenesis.Journal of extracellular vesicles · 2025Article
- SAM486A-induced inhibition of AMD1: metabolic and epigenetic implications in non-small cell lung cancer cells.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Transcriptional analysis of metastatic hormone-naïve prostate cancer primary tumor biopsies reveals a relevant role for SOX11 in prostate cancer cell dissemination.Genome biology · 2025Article
- Genetically encoded fluorescent reporter for polyamines.Nature communications · 2025Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
64 authors at 17 institutions in 5 countries.
Amaia Zabala-Letona *CIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Amaia Arruabarrena-Aristorena *CIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Natalia Martín-MartínCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Sonia Fernandez-RuizCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
James D SutherlandCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Michelle ClasquinAGIOS Pharmaceuticals, Cambridge, USA.
Julen Tomas-CortazarCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Jose JimenezVall d'Hebron Institute of Oncology (VHIO), Universidad Autonoma de Barcelona, Barcelona, Spain.
Ines TorresDepartment of Pathology, Vall d'Hebron Hospital, Universitat Autónoma de Barcelona, Barcelona, Spain.
Phong QuangAGIOS Pharmaceuticals, Cambridge, USA.
Pilar Ximenez-EmbunSpanish National Cancer Research Centre, Madrid, Spain.
Ruzica BagoMRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland.
Aitziber Ugalde-OlanoDepartment of Pathology, Basurto University Hospital, 48013, Bilbao, Spain.
Ana Loizaga-IriarteDepartment of Urology, Basurto University Hospital, 48013, Bilbao, Spain.
Isabel Lacasa-ViscasillasDepartment of Urology, Basurto University Hospital, 48013, Bilbao, Spain.
Miguel UndaDepartment of Urology, Basurto University Hospital, 48013, Bilbao, Spain.
Verónica TorranoCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Diana CabreraCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Sebastiaan M van LiempdCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Ylenia CendonSpanish National Cancer Research Centre, Madrid, Spain.
Elena CastroSpanish National Cancer Research Centre, Madrid, Spain.
Stuart MurrayAGIOS Pharmaceuticals, Cambridge, USA.
Ajinkya RevandkarInstitute of Oncology Research (IOR) and Oncology Institute of Southern Switzerland (IOSI), Bellinzona CH 6500, Switzerland.
Andrea AlimontiInstitute of Oncology Research (IOR) and Oncology Institute of Southern Switzerland (IOSI), Bellinzona CH 6500, Switzerland.
Yinan ZhangDepartment of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Amelia BarnettAGIOS Pharmaceuticals, Cambridge, USA.
Gina LeinAGIOS Pharmaceuticals, Cambridge, USA.
David PirmanAGIOS Pharmaceuticals, Cambridge, USA.
Ana R CortazarCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Leire ArrealCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Ludmila PrudkinVall d'Hebron Institute of Oncology (VHIO), Universidad Autonoma de Barcelona, Barcelona, Spain.
Ianire AstobizaCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Lorea Valcarcel-JimenezCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Patricia Zuñiga-GarcíaCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Itziar Fernandez-DominguezCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Marco PivaCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Alfredo Caro-MaldonadoCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Pilar Sánchez-MosqueraCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Mireia Castillo-MartínDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Violeta SerraCIBERONC.
Naiara BerazaCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Antonio GentilellaLaboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain.
George ThomasLaboratory of Metabolism and Cancer, Catalan Institute of Oncology, ICO, Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain.
Mikel AzkargortaCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Felix ElortzaCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Rosa FarràsCentro de Investigación Príncipe Felipe, Eduardo Primo Yúfera 3, 46012 Valencia, Spain.
David OlmosSpanish National Cancer Research Centre, Madrid, Spain.
Alejo EfeyanSpanish National Cancer Research Centre, Madrid, Spain.
Juan AnguitaCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Javier MuñozSpanish National Cancer Research Centre, Madrid, Spain.
Juan M Falcón-PérezCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Rosa BarrioCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Teresa MacarullaCIBERONC.
Jose M MatoCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Maria L Martinez-ChantarCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Carlos Cordon-CardoDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Ana M AransayCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
Kevin MarksAGIOS Pharmaceuticals, Cambridge, USA.
José BaselgaHuman Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Josep TaberneroCIBERONC.
Paolo NuciforoVall d'Hebron Institute of Oncology (VHIO), Universidad Autonoma de Barcelona, Barcelona, Spain.
Brendan D ManningDepartment of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Katya MarjonAGIOS Pharmaceuticals, Cambridge, USA.
Arkaitz CarracedoCIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
CIC bioGUNE · ESAgios Pharmaceuticals (United States) · USSpanish National Cancer Research Centre · ESUniversitat Autònoma de Barcelona · ESHospital de Basurto · ESInstituto de Salud Carlos III · ESCentro de Investigación Biomédica en Red de Cáncer · ESCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESHarvard University · USInstitut Català d'Oncologia · ESInstitute of Oncology Research · CHCentro de Investigacion Principe Felipe · ESChampalimaud Foundation · PTIcahn School of Medicine at Mount Sinai · USMemorial Sloan Kettering Cancer Center · USUniversity of Dundee · GBUniversity of the Basque Country · ES
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MScientific ReagentsP01CA087497 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI PETRINI, JOHN HJ · 2000 to 2021
$35.4MDecoding and Targeting the PI3K-mTOR Signaling Network in CancerR35CA197459 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI BRENDAN D. MANNING · 2015 to 2026
$10.8MRole of SAMe in Pathogenesis and Treatment of Non-Alcholic Fatty Liver DiseaseR01AT001576 · NCCIH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LU, SHELLY CHI-LOO · 2002 to 2018
$5.0MThe Function of rpL5 and rpL11 in induction of p53R01CA158768 · NCI · UNIVERSITY OF CINCINNATI · PI THOMAS, GEORGE · 2012 to 2017
$1.5MEuropean Research Council 336343Medical Research Council MC_UU_12016/2NCCIH NIH HHS R01 AT001576NCI NIH HHS P01 CA087497NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA158768NCI NIH HHS R35 CA197459
Abstract
Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation is validated in mouse and human cancer specimens. AMD1 is upregulated in human prostate cancer with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibit a predominant decrease in AMD1 immunoreactivity that is associated with a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program.
Indexed as
Adenosylmethionine DecarboxylaseAnimalsCell ProliferationEnzyme ActivationEverolimusHumansMaleMechanistic Target of Rapamycin Complex 1MetabolomicsMiceMultiprotein ComplexesPhosphatidylinositol 3-KinasesPolyaminesProstatic NeoplasmsProtein StabilityPTEN PhosphohydrolaseAdenosylmethionine DecarboxylaseAMD1 protein, humanEverolimusMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesPhosphatidylinositol 3-KinasesPolyaminesPTEN PhosphohydrolasePTEN protein, humanS-adenosyl-3-methylthiopropylamineS-AdenosylmethionineTOR Serine-Threonine Kinases
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