No conflicts of interest were declared.
Fibulin-3 is associated with tumour progression and a poor prognosis in nasopharyngeal carcinomas and inhibits cell migration and invasion via suppressed AKT activity†
Article first published online: 6 OCT 2010
Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 222, Issue 4, pages 367–379, December 2010
How to Cite
Hwang, C.-F., Chien, C.-Y., Huang, S.-C., Yin, Y.-F., Huang, C.-C., Fang, F.-M., Tsai, H.-T., Su, L.-J. and Chen, C.-H. (2010), Fibulin-3 is associated with tumour progression and a poor prognosis in nasopharyngeal carcinomas and inhibits cell migration and invasion via suppressed AKT activity. J. Pathol., 222: 367–379. doi: 10.1002/path.2776
- Issue published online: 25 OCT 2010
- Article first published online: 6 OCT 2010
- Accepted manuscript online: 7 SEP 2010 12:00AM EST
- Manuscript Accepted: 1 SEP 2010
- Manuscript Revised: 23 AUG 2010
- Manuscript Received: 24 MAR 2010
- nasopharyngeal carcinoma;
Nasopharyngeal carcinoma (NPC) is known for its highly metastatic character. Recent advances in diagnosis and treatment have not improved the high mortality rate that is attributable to early metastasis. Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. We demonstrate comprehensively that fibulin-3 is down-regulated in NPC. Loss of fibulin-3 expression is significantly correlated with advanced tumour and lymph node-metastasis stages, and indicates a poor 5-year survival rate. Functionally, fibulin-3 has the ability to suppress cell migration and invasion in NPC cancer cells by decreasing the activity of phospho-AKT. Conversely, its depletion by fibulin-3-mediated siRNAs may elevate phospho-AKT activity and significantly enhance the ability of NPC cancer cells to migrate and invade. Consistent with this negative association between fibulin-3 and phospho-AKT, their expression levels are inversely correlated in NPC specimens by immunohistochemical analysis. Thus, lower fibulin-3 expression is an important indicator of poor survival. It may also contribute to the development of new therapeutic strategies to block the PI3K/AKT pathway in NPC cancer cells. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.