Abstract
BackgroundNasopharyngeal carcinoma (NPC) is known for its high metastatic potential and locoregional recurrence, although the molecular alterations that are driving NPC metastasis remain unclear at this time. This study aimed to examine the expression of fibulin-5 in NPC, correlate the results with clinicopathological variables and survival, and to investigate the role of fibulin-5 in human NPC cell lines.Material and MethodsStandard semi-quantitative-RT-PCR, quantitative-RT-PCR, immunoblotting, and immunohistochemistry were used to investigate the mRNA and protein expression profiles of fibulin-5 in normal and NPC tissues. Immunohistochemistry of fibulin-5 was correlated with clinicopathological characteristics by univariate analyses. NPC cells overexpressing fibulin-5 or fibulin-5-siRNA cells were generated by stable transfection to characterize the molecular mechanisms of fibulin-5-elicited cell growth and metastasis.ResultsOur results demonstrated that fibulin-5 overexpression in NPC specimens and significantly correlated with advanced tumor metastasis indicating a poor 5-year overall survival. Fibulin-5 was mainly expressed in the nucleus in human NPC specimens and cell lines. Functionally, fibulin-5 overexpression yielded fast growth in NPC cells. In addition, fibulin-5 promotes cell metastasis in NPC cells through increased FLJ10540 and phosphor-AKT activity. In contrast, siRNA depletion of fibulin-5 suppressed FLJ10540 expression and phosphor-AKT activity. Suppression of either fibulin-5 or FLJ10540 can cause significant inhibition with regards to cell motility in NPC cells. Finally, immunohistochemical analysis of human aggressive NPC specimens showed a significant and positive correlation between fibulin-5 and FLJ10540 expression.ConclusionHigher fibulin-5 expression is not only an important indicator of poor survival, but also contributes to the development of new therapeutic strategies in the FLJ10540/AKT pathway for NPC treatment.
Highlights
Nasopharyngeal carcinoma (NPC) arises from the epithelial cells that cover the surface and line the nasopharynx [1]
Fibulin-5 was overexpressed in NPC specimens To determine whether fibulin-5 participates in the pathogenesis of NPC, semi-quantitative RT-PCR and Q-RTPCR were performed on 6 NPC-tumor and 3 normal tissue samples
Expression of fibulin-5 in another batch of freshly frozen tumor and normal samples was verified by western blotting, the results of which were consistent with the observed mRNA expression of fibulin-5 (Figure 1C)
Summary
Nasopharyngeal carcinoma (NPC) arises from the epithelial cells that cover the surface and line the nasopharynx [1]. The molecular mechanisms of the progression and metastasis of NPC remain unclear at this time. NPC cells overexpressing fibulin-5 or fibulin-5-siRNA cells were generated by stable transfection to characterize the molecular mechanisms of fibulin-5-elicited cell growth and metastasis. Results: Our results demonstrated that fibulin-5 overexpression in NPC specimens and significantly correlated with advanced tumor metastasis indicating a poor 5-year overall survival. Fibulin-5 was mainly expressed in the nucleus in human NPC specimens and cell lines. Fibulin-5 promotes cell metastasis in NPC cells through increased FLJ10540 and phosphor-AKT activity. Immunohistochemical analysis of human aggressive NPC specimens showed a significant and positive correlation between fibulin-5 and FLJ10540 expression. Conclusion: Higher fibulin-5 expression is an important indicator of poor survival, and contributes to the development of new therapeutic strategies in the FLJ10540/AKT pathway for NPC treatment
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