Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
Biochem Biophys Res Commun. 2014 Feb 14;444(3):382-6. doi: 10.1016/j.bbrc.2014.01.064. Epub 2014 Jan 24.
The 14-3-3 family of proteins regulates various signaling pathways involved in cell cycle, apoptosis, stress response, and malignant transformation. We previously demonstrated that the β isoform of the 14-3-3 protein promotes cell growth and tumorigenicity of rat K2 hepatocellular carcinoma cells. We identified fourteen-three-three beta interactant 1 (FBI1)/Akirin2 as a binding partner of 14-3-3β and showed that the complex of these proteins promotes tumorigenicity and metastasis of K2 cells. In addition, we demonstrated that FBI1/Akirin2 downregulation shortened the duration of MAPK activity. Because 14-3-3β and FBI1/Akirin2 overexpression is observed in various cancer cell lines, 14-3-3β-FBI1/Akirin2 oncogenic function should be elucidated in different types of cancer. In this study, we used LLC1 Lewis lung carcinoma cells as a model. We established FBI1/Akirin2 knockdown cell clones through transfection of an antisense FBI1/Akirin2 expression vector and assessed the capacity for cell growth in vitro and tumorigenicity and metastasis in vivo. FBI1/Akirin2 downregulation decreased anchorage-independent growth, whereas the growth rate in monolayer culture was not affected. Moreover, an in vivo assay in nude mice showed that FBI1/Akirin2 overexpression is required for LLC1 tumor growth and metastasis. These results suggest that FBI1/Akirin2 plays an important role in oncogenesis of LLC1 lung carcinoma cells, and this protein may also serve as an oncogene in other cancers.
蛋白质 14-3-3 家族调节参与细胞周期、细胞凋亡、应激反应和恶性转化的各种信号通路。我们之前证明，14-3-3 蛋白的β同工型促进大鼠 K2 肝细胞癌细胞的细胞生长和致瘤性。我们鉴定出十四三-三-β相互作用蛋白 1（FBI1）/Akirin2 是 14-3-3β的结合伴侣，并表明这些蛋白质的复合物促进 K2 细胞的致瘤性和转移。此外，我们证明 FBI1/Akirin2 的下调缩短了 MAPK 活性的持续时间。由于在各种癌细胞系中观察到 14-3-3β和 FBI1/Akirin2 的过表达，因此应在不同类型的癌症中阐明 14-3-3β-FBI1/Akirin2 的致癌功能。在这项研究中，我们使用 LLC1 Lewis 肺癌细胞作为模型。我们通过转染反义 FBI1/Akirin2 表达载体建立了 FBI1/Akirin2 敲低细胞克隆，并评估了体外细胞生长、体内致瘤性和转移能力。FBI1/Akirin2 的下调降低了锚定非依赖性生长，而单层培养中的生长速度不受影响。此外，裸鼠体内实验表明，FBI1/Akirin2 的过表达是 LLC1 肿瘤生长和转移所必需的。这些结果表明，FBI1/Akirin2 在 LLC1 肺癌细胞的致癌作用中发挥重要作用，并且该蛋白也可能在其他癌症中作为癌基因。
