Abstract

An altered metabolism is involved in the development of clear cell - renal cell carcinoma (ccRCC), and in this tumor many altered genes play a fundamental role in controlling cell metabolic activities. We delineated a large-scale metabolomic profile of human ccRCC, and integrated it with transcriptomic data to connect the variations in cancer metabolism with gene expression changes. Moreover, to better analyze the specific contribution of metabolic gene alterations potentially associated with tumorigenesis and tumor progression, we evaluated the transcription profile of primary renal tumor cells. Untargeted metabolomic analysis revealed a signature of an increased glucose uptake and utilization in ccRCC. In addition, metabolites related to pentose phosphate pathway were also altered in the tumor samples in association with changes in Krebs cycle intermediates and related metabolites. We identified NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) as the most highly expressed gene in renal cancer cells and evaluated its role in sustaining angiogenesis, chemoresistance, and mitochondrial dysfunction. Finally, we showed that silencing of NDUFA4L2 affects cell viability, increases mitochondrial mass, and induces ROS generation in hypoxia.

Autore Pugliese

• Napoli Anna , Simone Cristiano , Ribatti Domenico , Maiorano Eugenio , Sallustio Fabio , Battaglia Michele , Ditonno Pasquale

Tutti gli autori

• GIGLIO A.;NAPOLI A.;SIMONE C.;RIBATTI D.;RANIERI E.;MAIORANO E.;SALLUSTIO F.;LUCARELLI G.;SERINO G.;LEPORE SIGNORILE M.;BATTAGLIA M.;RUTIGLIANO M.;SANESE P.;DITONNO P.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2018

ISSN

1945-4589

ISBN

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Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

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Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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