ArticleCell death & disease2016
TRAP1 downregulation in human ovarian cancer enhances invasion and epithelial-mesenchymal transition.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Restricting metabolic plasticity enhances stress adaptation through the modulation of PDH and HIF1A in TRAP1-depleted colon cancer.Cancer letters · 2025Article
- Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer.Histology and histopathology · 2025Article
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- An EMT-based gene signature enhances the clinical understanding and prognostic prediction of patients with ovarian cancers.Journal of ovarian research · 2023Article
- ACancer research communications · 2023Article
- Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer.Frontiers in oncology · 2023Article
- The development of cancers research based on mitochondrial heat shock protein 90.Frontiers in oncology · 2023Review
- Regulation of mitochondrial complex III activity and assembly by TRAP1 in cancer cells.Cancer cell international · 2022Article
- Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer.Cancer letters · 2022Article
- Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion.Cell death & disease · 2022Review
- Ruscogenin attenuated tight junction injury and tumor migration in colorectal liver metastasis mice via regulating TRAP1.Translational cancer research · 2021Article
- Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy.Frontiers in oncology · 2021Review
- TRAP1 Regulates Wnt/β-Catenin Pathway through LRP5/6 Receptors Expression Modulation.International journal of molecular sciences · 2020Article
- Review
- Article
- Dynamically Shaping Chaperones. Allosteric Modulators of HSP90 Family as Regulatory Tools of Cell Metabolism in Neoplastic Progression.Frontiers in oncology · 2020Review
- HSPA1A, HSPA1L and TRAP1 heat shock genes may be associated with prognosis in ovarian epithelial cancer.Oncology letters · 2020Article
- The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy.Frontiers in oncology · 2020Review
- Gene Copy Number and Post-Transductional Mechanisms Regulate TRAP1 Expression in Human Colorectal Carcinomas.International journal of molecular sciences · 2019Article
- Network vulnerability-based and knowledge-guided identification of microRNA biomarkers indicating platinum resistance in high-grade serous ovarian cancer.Clinical and translational medicine · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer (OC) is the second leading cause of gynecological cancer death worldwide. Although the list of biomarkers is still growing, molecular mechanisms involved in OC development and progression remain elusive. We recently demonstrated that lower expression of the molecular chaperone TRAP1 in OC patients correlates with higher tumor grade and stage, and platinum resistance. Herein we show that TRAP1 is often deleted in high-grade serous OC patients (N=579), and that TRAP1 expression is correlated with the copy number, suggesting this could be one of the driving mechanisms for the loss of TRAP1 expression in OC. At molecular level, downregulation of TRAP1 associates with higher expression of p70S6K, a kinase frequently active in OC with emerging roles in cell migration and tumor metastasis. Indeed, TRAP1 silencing in different OC cells induces upregulation of p70S6K expression and activity, enhancement of cell motility and epithelial-mesenchymal transition (EMT). Consistently, in a large cohort of OC patients, TRAP1 expression is reduced in tumor metastases and directly correlates with the epithelial marker E-Cadherin, whereas it inversely correlates with the transcription factor Slug and the matrix metallopeptidases 2 and 9. Strikingly, pharmacological inhibition of p70S6K reverts the high motility phenotype of TRAP1 knock-down cells. However, although p70S6K inhibition or silencing reduces the expression of the transcription factors Snail and Slug, thus inducing upregulation of E-Cadherin expression, it is unable to revert EMT induced by TRAP1 silencing; furthermore, p70S6K did not show any significant correlation with EMT genes in patients, nor with overall survival or tumor stage, suggesting an independent and predominant role for TRAP1 in OC progression. Altogether, these results may provide novel approaches in OC with reduced TRAP1 expression, which could be resistant to therapeutic strategies based on the inhibition of the p70S6K pathway, with potential future intervention in OC invasion and metastasis.
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