TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor

Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to tumor outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a molecular chaperone involved in the regulation of energetic metabolism in cancer cells. This protein is highly expressed in several cancers, such as glioblastoma, colon, breast, prostate and lung cancers and is often associated with drug resistance. However, TRAP1 is also downregulated in specific tumors, such as ovarian, bladder and renal cancers, where its lower expression is correlated with the worst prognoses and chemoresistance. TRAP1 is the only mitochondrial member of the Heat Shock Protein 90 (HSP90) family that directly interacts with respiratory complexes, contributing to their stability and activity but it is still unclear if such interactions lead to reduced or increased respiratory capacity. The role of TRAP1 is to enhance or suppress oxidative phosphorylation; the effects of such regulation on tumor development and progression are controversial. These observations encourage the study of the mechanisms responsible for the dualist role of TRAP1 as an oncogene or oncosuppressor in specific tumor types. In this review, TRAP1 puzzling functions were recapitulated with a special focus on the correlation between metabolic reprogramming and tumor outcome. We wanted to investigate whether metabolism-targeting drugs can efficiently interfere with tumor progression and whether they might be combined with chemotherapeutics or molecular-targeted agents to counteract drug resistance and reduce therapeutic failure.

Genes. 2018 Apr 05*** epublish ***

Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Matteo Landriscina, Franca Esposito

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy. ., Institute of Protein Biochemistry (IBP), National Research Council, 80131 Naples, Italy. ., Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain. ., Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 7100 Foggia, Italy. ., Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy. .

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