a Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University , Changsha , Hunan , China.
Cancer Biol Ther. 2017 Sep 2;18(9):715-722. doi: 10.1080/15384047.2017.1360445.
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.
肺腺癌 (LUAD) 是肺癌最常见的组织学亚型,仍然是全球癌症死亡的主要原因。迫切需要发现更敏感和特异的新型靶向生物标志物来预测 LUAD 的发生和进展。Flotillin-1 (Flot-1) 已被报道在几种肿瘤类型的进展中具有重要作用,但在 LUAD 的进展中尚未报道。在这里,我们证明 flotillin-1 的表达在 5 种 LUAD 细胞中上调。此外,还采用多种方法探索 flotillin-1 在 LUAD 细胞系中的致瘤性。通过过表达和基于 siRNA 的敲低后,通过免疫印迹分析 flotillin-1 的表达水平。细胞增殖、划痕愈合、Transwell 迁移和 Matrigel 侵袭以及异种移植肿瘤生长测定用于确定 flotillin-1 在 LUAD 进展中的作用。Flotillin-1 的下调逆转了,而 flotillin-1 的上调增强了 LUAD 细胞的恶性表型体外。一致地,与转染空载体的细胞相比, flotillin-1 敲低的细胞在裸鼠中形成的肿瘤较小。此外,与 flotillin-1 沉默组相比,对照组在 LUAD 的异种移植模型中表现出明显更强的致瘤作用。总之,有结论表明 flotillin-1 是一种致癌蛋白,在促进 LUAD 的增殖和致瘤性方面发挥重要作用,提示 flotillin-1 可能代表 LUAD 的一种新的治疗靶点。