Liu Li, Zhang Qingling, Zhang Yanfei, Wang Shuang, Ding Yanqing
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Neoplasia. 2006 Nov;8(11):917-24. doi: 10.1593/neo.06364.
T lymphoma invasion and metastasis 1 (Tiam1) is a metastasis-related gene of T lymphoma that is also involved in the metastasis of a variety of other cancers. In this study, we tested the hypothesis that Tiam1 is a determinant of proliferation and metastasis in colorectal cancer, and we examined the effect of the inhibition of Tiam1 expression on proliferation and metastasis. We succeeded in establishing the Tiam1 knockdown colorectal cancer cell line using human immunodeficiency virus lentivirus-mediated RNA interference (RNAi) and found that the silencing of Tiam1 resulted in the effective inhibition of in vitro cell growth and of the invasive ability of colorectal cancer cells. Using an orthotopic xenograft model in nude mice, we confirmed that Tiam1 silencing could reduce tumor growth by subcutaneous injection and could suppress lung and liver metastases of colorectal cancer cells. Our results suggest that Tiam1 truly plays a causal role in the metastasis of colorectal cancer and that RNAi-mediated silencing of Tiam1 may provide an opportunity to develop a new treatment strategy for colorectal cancer.
T淋巴瘤侵袭与转移1(Tiam1)是T淋巴瘤的一个与转移相关的基因,也参与多种其他癌症的转移。在本研究中,我们检验了Tiam1是结直肠癌增殖和转移的决定因素这一假说,并研究了抑制Tiam1表达对增殖和转移的影响。我们成功利用人类免疫缺陷病毒慢病毒介导的RNA干扰(RNAi)建立了Tiam1基因敲低的结直肠癌细胞系,发现Tiam1基因沉默有效抑制了体外细胞生长以及结直肠癌细胞的侵袭能力。利用裸鼠原位异种移植模型,我们证实Tiam1基因沉默可通过皮下注射减少肿瘤生长,并可抑制结直肠癌细胞的肺转移和肝转移。我们的结果表明,Tiam1在结直肠癌转移中确实起因果作用,RNAi介导的Tiam1基因沉默可能为开发结直肠癌新治疗策略提供契机。