Centrosomal protein 55 activates NF-κB signalling and promotes pancreatic cancer cells aggressiveness
Abstract Centrosomal protein 55 (CEP55) is a microtubule-bundling protein that participants in cell mitosis. It is overexpressed in several solid tumours and promotes the growth and invasion of cancer cells. However, the role of CEP55 in pancreatic cancer (PANC) remains unclear. Herein, upregulated...
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| Autores principales: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/8617f4b80f9240a28f206e041b2c95f0 |
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| Sumario: | Abstract Centrosomal protein 55 (CEP55) is a microtubule-bundling protein that participants in cell mitosis. It is overexpressed in several solid tumours and promotes the growth and invasion of cancer cells. However, the role of CEP55 in pancreatic cancer (PANC) remains unclear. Herein, upregulated expression of CEP55 (associated with poor prognosis) was detected in PANC using quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry. Cell migration, colony formation, wound-healing, and Transwell matrix penetration assays, revealed that upregulation of CEP55 promoted PANC cells proliferation, migration, and invasion in vitro, whereas knockdown of CEP55 attenuated it. In an in vivo murine model, CEP55 overexpression accelerated PANC cells tumourigenicity, together with upregulation of the protein levels of invasion-related proteins matrix metalloproteinase (MMP)2, MMP9, and proliferation-related protein Cyclin D1. Downregulation of CEP55 had the reverse effect. Moreover, the nuclear factor κB (NF-κB)/IκBα signalling pathway, which was activated in CEP55-transduced PANC cells and inhibited in CEP55-silenced PANC cells, contributed to CEP55-mediated PANC cell aggressiveness. This study provided new insights into the oncogenic roles of CEP55 and the mechanism by which the NF-κB pathway is hyperactivated in patients with PANC, indicating that CEP55 is a valuable prognostic factor and a potential therapeutic target in PANC. |
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