Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/62002

TitleNuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer
Author(s)Zecchini, Vincent
Madhu, Basetti
Russell, Roslin
Pértega-Gomes, Nelma
Warren, Anne
Gaude, Edoardo
Borlido, Joana
Stark, Rory
Ireland-Zecchini, Heather
Rao, Roheet
Scott, Helen
Boren, Joan
Massie, Charlie
Asim, Mohammad
Brindle, Kevin
Griffiths, John
Frezza, Christian
Neal, David E.
Mills, Ian G.
KeywordsArrestins
Chromatin Immunoprecipitation
Fluorescent Antibody Technique
Fumarate Hydratase
Gas Chromatography-Mass Spectrometry
Gene Expression Profiling
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Immunoblotting
Immunohistochemistry
Magnetic Resonance Spectroscopy
Male
Metabolic Networks and Pathways
Metabolomics
Prostatic Neoplasms
RNA Interference
Succinate Dehydrogenase
Tissue Array Analysis
beta-Arrestin 1
beta-Arrestins
Models, Biological
Adaptor
hypoxia
metabolism
prostate
transcription
Issue date17-Jun-2014
PublisherEMBO
JournalEmbo Journal
CitationZecchini, V., Madhu, B., Russell, R., Pértega‐Gomes, N., et. al. (2014). Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer. The EMBO journal, 33(12), 1365-1382.
Abstract(s)Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.
TypeArticle
URIhttp://hdl.handle.net/1822/62002
DOI10.15252/embj.201386874
ISSN0261-4189
e-ISSN1460-2075
Publisher versionhttps://www.embopress.org/doi/full/10.15252/embj.201386874
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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