Dataset Information

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.

ABSTRACT: Cholangiocarcinoma (CCA) is a deadly tumour lacking effective therapies. Clinically-relevant experimental models and analysis of human samples represent the cornerstone of mechanistic cancer research. Thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats encompasses key histological and molecular features of human iCCA. Molecular studies in bile may capture carcinogenic alterations and therapeutic vulnerabilities in CCA. We performed bile proteomic and metabolomic analyses in this model leading us to identify unrecognized mechanisms relevant to human iCCA.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Cholangiocarcinoma

SUBMITTER: Antonio Ramos Fernández

LAB HEAD: Matías A. Ávila

PROVIDER: PXD032802 | Pride | 2022-06-09

REPOSITORIES: Pride

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Publications

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.

Colyn Leticia L Alvarez-Sola Gloria G Latasa M Ujue MU Uriarte Iker I Herranz Jose M JM Arechederra Maria M Vlachogiannis George G Rae Colin C Pineda-Lucena Antonio A Casadei-Gardini Andrea A Pedica Federica F Aldrighetti Luca L López-López Angeles A López-Gonzálvez Angeles A Barbas Coral C Ciordia Sergio S Van Liempd Sebastiaan M SM Falcón-Pérez Juan M JM Urman Jesus J Sangro Bruno B Vicent Silve S Iraburu Maria J MJ Prosper Felipe F Nelson Leonard J LJ Banales Jesus M JM Martinez-Chantar Maria Luz ML Marin Jose J G JJG Braconi Chiara C Trautwein Christian C Corrales Fernando J FJ Cubero F Javier FJ Berasain Carmen C Fernandez-Barrena Maite G MG Avila Matias A MA

Journal of experimental & clinical cancer research : CR 20220526 1

<h4>Background</h4>Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA.<h4>Methods</h4>Cholangiocarcinogenesis was induced in rats (TAA) and ...[more]

PMID: 35619118

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Project description:Fruit ripening is a very important physiological process which gains relevance in crop species due to their economical and nutritional repercussions. During fruit ripening enormous metabolic changes occur in a genetically-controlled scenario affecting the physiology of most cell compartments. Peroxisomes are single-membrane bounded organelles present in all eukaryotes which display a noteworthy nitro-oxidative metabolism, and harbor catalase as one of the major antioxidant enzymes in cells. Quantitative proteomics analysis by isobaric tags for relative and absolute quantification (iTRAQ) was used to investigate the ripening process in sweet pepper (Capsicum annuum L.) fruits. Out of 2,574 quantified proteins, 692 were found to be significantly more abundant in immature green fruits compared to red ones, but 497 showed a lower expression as the ripening proceeded. Overall, about 50% of the detectable proteins were estimated to modify their expression due to the ripening process. Data obtained from the Gene Ontology algorithms (AgriGO platform) showed that from all the identified proteins, 46 (2%) were only predicted to have a peroxisomal origin, with a high number of them displaying up-expression tendency during ripening. Catalase was framed within the group which showed lower expression in ripe fruits, but this enzyme was also susceptible to undergo posttranslational modifications (PTMs) promoted by reactive nitrogen and oxygen species (RNS and ROS) through nitration, S-nitrosylation and oxidation events which provoked its inhibition. The biochemical characterization of catalase indicates that it has atypical native molecular mass (125-135 kDa), since it behaves as a homodimer, and isoelectric point of 7.4, which is higher than that of the majority of plant catalases reported so far. Taking together, these data suggest that ROS and RNS could be essential to modulate the role of catalase for the maintenance of basic cellular peroxisomal functions during pepper fruit ripening where nitro-oxidative stress occur.

Dataset Information

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.

Publications

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.

Similar Datasets

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