Oncogenic Fibulin-5 Promotes Nasopharyngeal Carcinoma Cell Metastasis through the FLJ10540/AKT Pathway and Correlates with Poor Prognosis

• Published in: PloS one Vol. 8; no. 12; p. e84218
• Main Authors: Hwang, Chung-Feng, Shiu, Li-Yen, Su, Li-Jen, Yu-Fang Yin, Wang, Wei-Sheng, Huang, Shun-Chen, Chiu, Tai-Jan, Huang, Chao-Cheng, Zhen, Yen-Yi, Tsai, Hsin-Ting, Fang, Fu-Min, Huang, Tai-Lin, Chen, Chang-Han
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.12.2013; Public Library of Science (PLoS)
• Subjects: Active Transport, Cell Nucleus; AKT protein; Biology and life sciences; Biopsy; Biotechnology; Cancer; Cancer metastasis; Carcinoma; Cell cycle; Cell Cycle Proteins - metabolism; Cell growth; Cell Line, Tumor; Cell Movement; Cell Nucleus - metabolism; Cell Proliferation; Cell survival; Disease Progression; Extracellular matrix; Extracellular Matrix Proteins - deficiency; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Hematology; Hospitals; Humans; Immunoblotting; Immunohistochemistry; Male; Medical prognosis; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Middle Aged; Molecular modelling; mRNA; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - diagnosis; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness; Neoplasm Metastasis; Nuclear Proteins - metabolism; Nuclei; Nuclei (cytology); Oncogenes; Oncology; Otolaryngology; Pathology; Patients; Physicians; Polymerase chain reaction; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; R&D; Research & development; Research and Analysis Methods; RNA; RNA, Small Interfering - genetics; Signal Transduction; siRNA; Survival; Survival Analysis; Throat cancer; Tissues; Transfection; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084218

Nasopharyngeal 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. Standard 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. 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. 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. Higher 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.