TRAP1 controls cell migration of cancer cells in metabolic stress conditions: Correlations with AKT/p70S6K pathways
| Autor: | Franca Esposito, Rosario Avolio, Maria Rosaria Amoroso, Leandra Sepe, Danilo Swann Matassa, Francesca Maddalena, Ilenia Agliarulo, Diana Arzeni, Giovanni Paolella, Maria Carla Ferrari, Matteo Landriscina, Lorenza Sisinni |
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| Přispěvatelé: | Agliarulo, Ilenia, Matassa, DANILO SWANN, Amoroso, MARIA ROSARIA, Francesca, Maddalena, Lorenza, Sisinni, Sepe, Leandra, Ferrari, MARIA CARLA, Arzeni, Diana, Avolio, Rosario, Paolella, Giovanni, Matteo, Landriscina, Esposito, Franca |
| Rok vydání: | 2015 |
| Předmět: |
AKT/p70S6K pathway
Epithelial-Mesenchymal Transition Morphogenesis Wound healing Motility P70-S6 Kinase 1 Biology Gene Expression Regulation Enzymologic TRAP1 Metastasis Small hairpin RNA Cell Movement Stress Physiological Cell Line Tumor Neoplasms Gene silencing Humans HSP90 Heat-Shock Proteins Neoplasm Metastasis Protein kinase B Molecular Biology Ribosomal Protein S6 Kinases 70-kDa Cell migration Cell Biology Cell biology Gene Expression Regulation Neoplastic Colorectal carcinoma HEK293 Cells Cancer cell Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1853(10):2570-2579 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2015.05.034 |
| Popis: | Cell motility is a highly dynamic phenomenon that is essential to physiological processes such as morphogenesis, wound healing and immune response, but also involved in pathological conditions such as metastatic dissemination of cancers. The involvement of the molecular chaperone TRAP1 in the regulation of cell motility, although still controversial, has been recently investigated along with some well-characterized roles in cancer cell survival and drug resistance in several tumour types. Among different functions, TRAP1-dependent regulation of protein synthesis seems to be involved in the migratory behaviour of cancer cells and, interestingly, the expression of p70S6K, a kinase responsible for translation initiation, playing a role in cell motility, is regulated by TRAP1. In this study, we demonstrate that TRAP1 silencing enhances cell motility in vitro but compromises the ability of cells to overcome stress conditions, and that this effect is mediated by the AKT/p70S6K pathway. In fact: i) inhibition of p70S6K activity specifically reduces migration in TRAP1 knock-down cells; ii) nutrient deprivation affects p70S6K activity thereby impairing cell migration only in TRAP1-deficient cells; iii) TRAP1 regulates the expression of both AKT and p70S6K at post-transcriptional level; and iii) TRAP1 silencing modulates the expression of genes involved in cell motility and epithelial–mesenchymal transition. Notably, a correlation between TRAP1 and AKT expression is found in vivo in human colorectal tumours. These results provide new insights into TRAP1 role in the regulation of cell migration in cancer cells, tumour progression and metastatic mechanisms. |
| Databáze: | OpenAIRE |
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