ArticleCancer cell2016
Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming.
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Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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115citing papers in PubMed
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Who cites it
115 citing papers in PubMed, 214 citations in OpenAlex.
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- Investigating hypoxia-inducible factor signaling in cancer: Mechanisms, clinical implications, targeted therapeutic strategies, and resistance.Cancer pathogenesis and therapy · 2026Review
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- Mitochondrial dysfunction as a metabolic checkpoint of immunotherapy response in colorectal cancer.Frontiers in immunology · 2026Review
- Autophagy-Modulating Nanomedicine for Glioma: Delivery Barriers, Lysosomal Interactions, and a Flux-Resolved Translational Decision Framework.International journal of nanomedicine · 2026Review
- Photobiomodulation promotes osteogenic differentiation of mesenchymal stem cells and increases P-Akt levels in vitro.Scientific reports · 2025Article
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- Delayed viral clearance and altered inflammatory responses affect severity of SARS-CoV-2 infection in aged mice.Immunity & ageing : I & A · 2025Article
- V-ATPase in glioma stem cells: a novel metabolic vulnerability.Journal of experimental & clinical cancer research : CR · 2025Article
- Resveratrol relieves myocardial ischemia-reperfusion injury through inhibiting AKT nitration modification.Redox report : communications in free radical research · 2024Article
- Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.Nature reviews. Urology · 2024Review
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- CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transcriptional regulation and post-translational modifications in the glycolytic pathway for targeted cancer therapy.Acta pharmacologica Sinica · 2024Review
- PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.Genes & diseases · 2024Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 8 institutions in 3 countries.
Young Chan ChaeProstate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Valentina VairaIstituto Nazionale Genetica Molecolare "Romeo and Enrica Invernizzi", Milan 20122, Italy; Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy.
M Cecilia CainoProstate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Hsin-Yao TangDepartment of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy.
Jae Ho SeoProstate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Andrew V KossenkovCenter for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA 19104, USA.
Luisa OttobriniDepartment of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; Institute for Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Milan 20090, Italy.
Cristina MartelliDepartment of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy.
Giovanni LucignaniDepartment of Health Sciences, University of Milan, Milan 20142, Italy; Department of Diagnostic Services, Unit of Nuclear Medicine, San Paolo Hospital, Milan 20142, Italy.
Irene BertoliniDivision of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy.
Marco LocatelliDivision of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
Kelly G BryantProstate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Jagadish C GhoshProstate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Sofia LisantiProstate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Bonsu KuFunctional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
Silvano BosariDivision of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy.
Lucia R LanguinoDepartment of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
David W SpeicherCenter for Systems and Computational Biology, The Wistar Institute, Philadelphia, PA 19104, USA; Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Dario C AltieriProstate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. Electronic address: daltieri@wistar.org.
The Wistar Institute · USUniversity of Milan · ITFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITInstitute of Molecular Bioimaging and Physiology · ITIstituto Nazionale Genetica Molecolare · ITKorea Research Institute of Bioscience and Biotechnology · KROspedale San Paolo · ITThomas Jefferson University · US
Funding
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9MTRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3MRole of Runx2 in prostate tumorigenesis and metastasisP01CA140043 · NCI · WISTAR INSTITUTE · PI ALTIERI, DARIO C · 2010 to 2021
$12.2MCONTROL OF APOPTOSIS IN CANCER BY SURVIVINR01CA078810 · NCI · YALE UNIVERSITY · PI ALTIERI, DARIO C · 1998 to 2017
$5.5MINTEGRIN SIGNALING PATHWAYS IN PROSTATE CANCERR01CA089720 · NCI · YALE UNIVERSITY · PI LANGUINO, LUCIA R. · 2001 to 2014
$2.8MIntegrative Approach to Comprehensive Analysis of High Throughput Data on a Cancer Center LevelR50CA211199 · NCI · WISTAR INSTITUTE · PI Andrew V Kossenkov · 2016 to 2026
$1.6M(PQC2) Plasticity Of The.PI3K Network In Early DormancyR01CA190027 · NCI · WISTAR INSTITUTE · PI ALTIERI, DARIO C · 2014 to 2016
$1.2MMitochondrial Hsp90s Regulation of Tumor Bioenergetics and MetastasisF32CA177018 · NCI · WISTAR INSTITUTE · PI CAINO, MARIA CECILIA · 2013 to 2015
$171kNCI NIH HHS F32 CA177018NCI NIH HHS P01 CA140043NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA078810NCI NIH HHS R01 CA089720NCI NIH HHS R01 CA190027NCI NIH HHS R50 CA211199NCI NIH HHS T32 CA009171
Abstract
Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an "actionable" therapeutic target in cancer.
Indexed as
AnimalsCell HypoxiaCell Line, TumorCell ProliferationCellular ReprogrammingFemaleHumansMaleMiceMice, Inbred NODMice, NudeMitochondriaNeoplasmsProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPyruvate Dehydrogenase Acetyl-Transferring KinasePDK1 protein, humanPdk1 protein, mouseProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPyruvate Dehydrogenase Acetyl-Transferring KinaseAkthypoxiametabolismmitochondriaPDK1tumor cell proliferation
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