Flotilin-1 promotes the tumorigenicity and progression of malignant phenotype in human lung adenocarcinoma
Flotilin-1 promotes the tumorigenicity and progression of malignant phenotype in human lung adenocarcinoma
复制标题
Flotilin-1促进人肺腺癌的致瘤性和恶性表型的进展
DOI：
10.1080/15384047.2017.1360445
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发表时间：
2017-01-01
影响因子：
3.6
通讯作者：
Zhang, Peng Fei
中科院分区：
文献类型：
--
作者：
Guo, Ai Yun;Liang, Xu Jun;Zhang, Peng Fei
肺腺癌（LUAD）是肺癌最常见的组织学亚型，也是全球癌症死亡的主要原因。发现更敏感和特异的新型靶生物标志物来预测LUAD的发生和发展是势在必行的。flotilin -1 （Flot-1）已被报道在几种肿瘤类型的进展中发挥重要作用，但在LUAD的进展中尚未报道。在这里，我们证明了flotilin -1的表达在5个LUAD细胞中上调。此外，采用多种方法探索flotilin -1在LUAD细胞系中的致瘤性。通过免疫印迹法分析flotilin -1过表达和sirna敲除后的表达水平。通过细胞增殖、划伤愈合、跨井迁移和基质侵袭以及异种移植物肿瘤生长试验来确定flotilin -1在LUAD进展中的作用。flotilin -1的下调被逆转，而flotilin -1的上调则增强了LUAD细胞的恶性表型。一致地，flotilin -1敲低的细胞在裸鼠体内形成的肿瘤比转染空载体的细胞更小。此外，在LUAD异种移植模型中，与flotillin-1沉默组相比，对照组表现出更强的致瘤作用。综上所述，flotilin -1是一种致瘤蛋白，在促进LUAD的增殖和致瘤性中起重要作用，提示flotilin -1可能是LUAD的一种新的治疗靶点。
ABSTRACT Lung adenocarcinoma (LUAD) accounts for the most common histological subtype of lung cancer which remains the leading cause of cancer death worldwide. The discovery of more sensitive and specific novel target biomarkers for predicting the development and progression of LUAD is imperative. Flotillin-1 (Flot-1) has been reported to have important roles in the progression of several tumor types but not been reported in the progression of LUAD. Here, we demonstrated that the expression of flotillin-1 was upregulated in 5 LUAD cells. Moreover, multiple approaches were used to explore the tumorigenicity of flotillin-1 in LUAD cell lines. The expression levels of flotillin-1 were analyzed by immunoblotting after overexpression and siRNA-based knockdown. Cell proliferation, scratch wound healing, transwell migration and matrigel invasion and xenograft tumor growth assays were used to determine the role of flotillin-1 in LUAD progression. Downregulation of flotillin-1 reversed, whereas upregulation of flotillin-1 enhanced, the malignant phenotype of LUAD cells in vitro. Consistently, cells with flotillin-1 knockdown formed smaller tumors in nude mice than cells transfected with the empty vector. Furthermore, the control group demonstrated significantly more tumorigenic effects compared to the flotillin-1-silenced group in the xenograft model of LUAD. In all, there draws a conclusion that flotillin-1 is a tumorigenic protein that plays an important role in promoting the proliferation and tumorigenicity of LUAD, suggesting that flotillin-1 may represent a novel the therapeutic target to LUAD.