RETRACTED: Oncogenic Fibulin-5 Promotes Nasopharyngeal Carcinoma Cell Metastasis through the FLJ10540/AKT Pathway and Correlates with Poor Prognosis (Retracted Article)

被引：42

作者：

Hwang, Chung-Feng ^{[1
,2
]}

Shiu, Li-Yen ^{[3
,4
]}

Su, Li-Jen ^{[5
]}

Yin, Yu-Fang ^{[1
,2
]}

Wang, Wei-Sheng ^{[1
,2
]}

Huang, Shun-Chen ^{[6
]}

Chiu, Tai-Jan ^{[7
]}

Huang, Chao-Cheng ^{[2
]}

Zhen, Yen-Yi ^{[8
,9
]}

Tsai, Hsin-Ting ^{[1
,2
]}

Fang, Fu-Min ^{[2
,10
]}

Huang, Tai-Lin ^{[7
]}

Chen, Chang-Han ^{[1
,2
,11
]}

机构：

[1] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Otolaryngol, Kaohsiung, Taiwan

[2] Kaohsiung Chang Gung Mem Hosp, Kaohsiung Chang Gung Head & Neck Oncol Grp, Kaohsiung, Taiwan

[3] Show Chwan Mem Hosp, Dept Med Res & Dev, Changhua, Taiwan

[4] Chang Bing Show Chwan Mem Hosp, Changhua, Taiwan

[5] Natl Cent Univ, Grad Inst Syst Biol & Bioinformat, Jhongli, Taiwan

[6] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Pathol, Kaohsiung, Taiwan

[7] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Hematol Oncol, Kaohsiung, Taiwan

[8] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Cardiol, Kaohsiung, Taiwan

[9] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan

[10] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Radiat Oncol, Kaohsiung, Taiwan

[11] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung, Taiwan

来源：

PLOS ONE | 2013年 / 8卷 / 12期

关键词：

EPSTEIN-BARR-VIRUS; TUMOR PROGRESSION; IN-VIVO; INVASION; EXPRESSION; CANCER; PROLIFERATION; MIGRATION; GROWTH; OVEREXPRESSION;

D O I：

10.1371/journal.pone.0084218

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: 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. Material and Methods: 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. 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. 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. Conclusion: 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.

引用

页数：18

共 39 条

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