Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer.

Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer.
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flotillin-1 表达升高与早期宫颈癌的淋巴结转移和不良预后相关。

DOI:
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发表时间:
2016
期刊:
Am J Cancer Res
影响因子:
--
通讯作者:
Song Libing
Song Libing
中科院分区:
其他
文献类型:
--
作者:
Li Zheng;Yang Yang;Gao Yang;Wu Xiaoliu;Yang Xielan;Zhu Yingjie;Yang Hongying;Wu Lin;Yang Chengang;Song Libing

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越来越多的证据表明,脂筏蛋白flotillin-1的表达在各种人类癌症中升高,但flotillin-1在宫颈癌发生中的作用仍不清楚。采用实时荧光定量PCR、免疫印迹和免疫组化(IHC)法检测宫颈癌细胞系和癌组织中flotillin-1的表达谱。采用免疫组化法检测308例石蜡包埋的宫颈癌组织中Flotilin-1蛋白的表达。采用异位表达和短发夹RNA干扰技术研究flotillin-1在宫颈癌细胞转移中的作用及其可能机制。Flotilin-1蛋白和mRNA在宫颈癌细胞系和癌组织中表达均显著上调; Flotilin-1蛋白在早期宫颈癌中的高表达与盆腔淋巴结转移显著相关(P < 0.001),是总生存期不良的独立预测因素。此外,Flotillin-1的上调和下调分别通过Wnt/β-catenin和核因子-κB(NF-κB)途径调节上皮-间质转化(EMT),显著影响宫颈癌细胞的运动和侵袭。我们的研究结果表明,Flotillin-1通过Wnt/β-catenin和NF-κB通路调节EMT促进宫颈癌细胞转移,Flotillin-1表达谱不仅是盆腔淋巴结转移的新预测因子,也是早期宫颈癌患者的近期危险因素。
Accumulating evidence has revealed that the expression of the lipid raft protein flotillin-1 is elevated in various human cancers, but the role flotillin-1 plays in the carcinogenesis of cervical cancer remains unclear. The expression profile of flotillin-1 was assayed using real-time PCR, western blotting, and immunohistochemical (IHC) staining in cervical cancer cell lines and cancer tissues with paired adjacent noncancerous cervical tissues. The expression of flotillin-1 protein was detected by IHC staining in a large cohort of 308 paraffin-embedded cervical cancer tissues. Ectopic expression and the short hairpin RNA interference approach were employed to determine the role of flotillin-1 in cervical cancer cell metastasis and the possible mechanism involved. Flotillin-1 expression protein and mRNA were significantly upregulated in cervical cancer cell lines and cancer tissues; elevated expression of flotillin-1 protein in early-stage cervical cancer was significantly associated with pelvic lymph node metastasis (P < 0.001), and was an independent predictive factor of poor overall survival. Moreover, flotillin-1 up- and downregulation remarkably affected cervical cancer cell motility and invasion, respectively, through epithelial-mesenchymal transition (EMT) regulated by the Wnt/β-catenin and nuclear factor-κB (NF-κB) pathways. Our results suggest that flotillin-1 facilitates cervical cancer cell metastasis through Wnt/β-catenin and NF-κB pathway-regulated EMT and that the flotillin-1 expression profile serves not only as novel predictor of pelvic lymph node metastasis, but also as neoteric risk factor for patients with early-stage cervical cancer.
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