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Mitochondria can receive, integrate, and transmit a variety of signals to shape many biochemical activities of the cell. In the process of tumor onset and growth, mitochondria contribute to the capability of cells of escaping death insults, handling changes in ROS levels, rewiring metabolism, and reprograming gene expression. Therefore, mitochondria can tune the bioenergetic and anabolic needs of neoplastic cells in a rapid and flexible way, and these adaptations are required for cell survival and proliferation in the fluctuating environment of a rapidly growing tumor mass. The molecular bases of pro-neoplastic mitochondrial adaptations are complex and only partially understood. Recently, the mitochondrial molecular chaperone TRAP1 (tumor necrosis factor receptor associated protein 1) was identified as a key regulator of mitochondrial bioenergetics in tumor cells, with a profound impact on neoplastic growth. In this review, we analyze these findings and discuss the possibility that targeting TRAP1 constitutes a new antitumor approach.
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http://dx.doi.org/10.3389/fonc.2017.00058 | DOI Listing |
RNA
September 2025
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, 80131, Italy;
Heat shock proteins have been increasingly identified in RNA-interactomes, suggesting potential roles beyond their canonical functions. Among those, the cancer-linked chaperone TRAP1 has been mainly characterized for its regulatory role on respiratory complex activity and protein synthesis, while its specific function as an RNA-binding protein (RBP) remains unclear. In this study, we confirmed the RNA-binding activity of TRAP1 in living cells using both protein- and RNA-centric approaches and demonstrated that multiple TRAP1 regions cooperate in such binding.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
August 2025
Institute of Neuroscience, National Research Council, via Ugo Bassi 58/B, Padova, 35131, Italy.
Background: Metabolic adaptations can sustain the pro-neoplastic functions exerted by macrophages in the tumor microenvironment. Malignant peripheral nerve sheath tumors (MPNSTs), aggressive and incurable sarcomas that develop either sporadically or in the context of the genetic syndrome Neurofibromatosis type 1, are highly infiltrated by macrophages, whose contribution to MPNST growth remains poorly characterized. Here, we analyze the role played by the molecular chaperone TRAP1, a regulator of mitochondrial metabolic pathways, in shaping the pro-tumoral activity of macrophages associated to MPNST cells.
View Article and Find Full Text PDFCancer Lett
August 2025
Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Electronic address:
Metabolic plasticity allows cancer cells to survive under adverse conditions. To investigate the role of mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 (TRAP1) in this process, we used CRISPR/Cas9 mediated genetic deletion to knock out (KO) TRAP1 in colon cancer cells. Depletion of TRAP1 triggered a series of events: induced metabolic reprogramming, increased glycolytic flux, downregulation of mitochondrial complex I, and elevated ROS generation.
View Article and Find Full Text PDFExp Mol Med
August 2025
School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
The majority of cancers remain incurable due to limited therapeutic responses in malignancies with high-risk genetic mutations such as TP53. Building on the success of mRNA vaccine technology, we investigated circular RNA (circRNA) therapeutics and identified hsa_circp53_0041947, a TP53-derived circRNA in multiple myeloma (MM). The hsa_circp53_0041947 encodes a functional peptide (circp53-209aa) demonstrating p53 mutation-independent anti-MM effects through CypD/TRAP1/HSP90 complex-mediated mechanisms.
View Article and Find Full Text PDFClin Ophthalmol
July 2025
Department of Ophthalmology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Background: Recent studies have demonstrated that mitochondrial dysfunction is pivotal in early diabetic retinopathy (DR). Tumor necrosis factor-associated protein 1 (TRAP1), a mitochondrial chaperone regulating stress responses, remains unexplored in DR pathogenesis.
Methods: We established in vivo and in vitro models of DR.