%0 Journal Article %T Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib %+ Université de Picardie Jules Verne (UPJV) %+ Centre Eugène Marquis (CRLCC) %+ Chemistry, Oncogenesis, Stress and Signaling (COSS) %+ CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE) %+ Laboratoire de Biochimie %+ CHU Amiens-Picardie %+ Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV) %+ Centre de recherches éducation et formation (CREF) %+ Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC) %+ Hôpital Jean Verdier [AP-HP] %+ Service d'Hépato-gastroentérologie %+ Institut Cochin (IC UM3 (UMR 8104 / U1016)) %A Houessinon, Aline %A Franois, Catherine %A Sauzay, Chloé %A Louandre, Christophe %A Mongelard, Gaelle %A Godin, Corinne %A Bodeau, Sandra %A Takahashi, Shinichiro %A Saidak, Zuzana %A Gutierrez, Laurent %A Regimbeau, Jean-Marc %A Barget, Nathalie %A Barbare, Jean-Claude %A Ganne, Nathalie %A Chauffert, Bruno %A Coriat, Romain %A Galmiche, Antoine %< avec comité de lecture %@ 1250-6559 %J Revue Européenne des Éléments Finis %I HERMÈS / LAVOISIER %V 15 %8 2016 %D 2016 %R 10.1186/s12943-016-0526-2 %Z Life Sciences [q-bio]Journal articles %X Background: Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking. Methods: We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib. Tumour explants prepared from surgical hepatocellular carcinoma (HCC) samples and serum samples obtained from HCC patients receiving sorafenib were also used. Results: We observed that genes of the metallothionein-1 (MT1) family are induced in the HCC cell line Huh7 exposed to sorafenib. Sorafenib increased the expression of MT1G mRNA in a panel of human cancer cells, an effect that was not observed with eight other clinically-approved kinase inhibitors. We identified the minimal region of the MT1G promoter that confers inducibility by sorafenib to a 133 base pair region containing an Anti-oxidant Response Element (ARE) and showed the essential role of the transcription factor NRF2 (Nuclear factor erythroid 2-Related Factor 2). We examined the clinical relevance of our findings by analysing the regulation of MT1G in five tumour explants prepared from surgical HCC samples. Finally, we showed that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and found an association with reduced overall survival. Conclusion: These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells. %G English %L hal-03589432 %U https://u-picardie.hal.science/hal-03589432 %~ UNIV-NANTES %~ UNIV-RENNES1 %~ CNRS %~ UNIV-PICARDIE %~ UNIV-PARIS10 %~ APHP %~ FNCLCC %~ MARQUIS %~ OSS %~ UR1-UFR-SVE %~ UR1-HAL %~ UPN %~ CREF %~ UR1-SDV %~ TEST-UR-CSS %~ UNIV-RENNES %~ UNIV-PARIS-LUMIERES %~ UNIV-PARIS %~ UP-SANTE %~ UR1-BIO-SA %~ UNIV-PARIS-NANTERRE %~ U-PICARDIE %~ CHIMERE %~ MP3CV %~ SSPC %~ NANTES-UNIVERSITE %~ UNIV-NANTES-AV2022