Hou Min, Tan Li, Wang Xia, Zhu Yun-Song
Department of Molecular Genetics, Shanghai Medical College, Fudan University and Key Laboratory of Molecular Medicine, Ministry of National Education, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2004 Aug;36(8):537-40. doi: 10.1093/abbs/36.8.537.
As a specific guanine nucleotide exchange factor of Rac1, Tiam1 (T-lymphoma invasion and metastasis inducing protein 1) is involved in a number of cellular events, such as cytoskeleton reorganization, cell adhesion, and cell migration. Since Tiam1 was implicated in the invasion and metastasis of T-lymphoma cells and breast tumor cells, we compared the expression level of Tiam1 in two human giant-cell lung carcinoma cell strains with high or low metastasis potential, and found that Tiam1 expression level in high-metastatic 95D cells was higher than that in low-metastatic 95C cells. To further confirm the role of Tiam1 in invasion and metastasis, we constructed the antisense Tiam1 expression plasmid (pcDNA3-anti-Tiam1), which was transfected into 95D cells. A stable transfected clone with decreased Tiam1 expression was screened and selected for further research. Transwell assay showed that down-regulation of endogenous Tiam1 by anti-Tiam1 can reduce the in vitro invasiveness of 95D cells. Our results suggested that Tiam1 signaling contributed to the invasion and metastasis of the human giant-cell lung carcinoma cells.
作为Rac1的一种特异性鸟嘌呤核苷酸交换因子,Tiam1(T淋巴瘤侵袭与转移诱导蛋白1)参与了许多细胞活动,如细胞骨架重组、细胞黏附及细胞迁移。由于Tiam1与T淋巴瘤细胞和乳腺肿瘤细胞的侵袭与转移有关,我们比较了两种具有高转移潜能或低转移潜能的人巨细胞肺癌细胞株中Tiam1的表达水平,发现高转移的95D细胞中Tiam1的表达水平高于低转移的95C细胞。为进一步证实Tiam1在侵袭和转移中的作用,我们构建了反义Tiam1表达质粒(pcDNA3-anti-Tiam1),并将其转染至95D细胞中。筛选并选择了一株Tiam1表达降低的稳定转染克隆用于进一步研究。Transwell实验表明,抗Tiam1下调内源性Tiam1可降低95D细胞的体外侵袭能力。我们的结果提示,Tiam1信号通路促进了人巨细胞肺癌细胞的侵袭与转移。