Fhit regulates invasion of lung tumor cells
Fhit regulates invasion of lung tumor cells
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DOI：
10.1038/onc.2009.418
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发表时间：
2010-02-25
期刊：
影响因子：
8
通讯作者：
Nawrocki-Raby, B.
中科院分区：
文献类型：
--
作者：
Joannes, A.;Bonnomet, A.;Nawrocki-Raby, B.
在许多类型的癌症中，脆弱的组氨酸三联体 (Fhit) 基因经常成为基因组改变的目标，导致基因和蛋白质表达减少或丢失。 Fhit 因其诱导细胞凋亡和抑制肿瘤细胞增殖的能力而被描述为肿瘤抑制基因。此外，一些研究表明Fhit表达缺乏与肿瘤侵袭性之间存在相关性，从而表明Fhit可能参与肿瘤进展。在这项研究中，我们探讨了 Fhit 在肿瘤细胞侵袭过程中的潜在作用。我们首先表明 Fhit 低表达与肿瘤细胞的体内和体外侵袭性相关。然后，我们发现，通过转染Fhit cDNA在Fhit阴性高侵袭性NCI-H1299细胞中过度表达Fhit，并通过转染Fhit小干扰RNA在Fhit阳性低侵袭性HBE4-E6/E7细胞中抑制Fhit，分别诱导迁移/侵袭能力的降低和增加。细胞行为的这些变化与紧密连接和粘附连接分子的重组以及基质金属蛋白酶和波形蛋白表达的调节有关。这些结果表明Fhit通过调节与上皮间质转化相关的基因的表达来控制肺肿瘤细胞的侵袭表型。癌基因 (2010) 29, 1203-1213; doi：10.1038/onc.2009.418； 2009 年 11 月 23 日在线发布
In many types of cancers, the fragile histidine triad (Fhit) gene is frequently targeted by genomic alterations leading to a decrease or loss of gene and protein expression. Fhit has been described as a tumor suppressor gene because of its ability to induce apoptosis and to inhibit proliferation of tumor cells. Moreover, several studies have shown a correlation between the lack of Fhit expression and tumor aggressiveness, thus suggesting that Fhit could be involved in tumor progression. In this study, we explored the potential role of Fhit during tumor cell invasion. We first showed that a low Fhit expression is associated with in vivo and in vitro invasiveness of tumor cells. Then, we showed that Fhit overexpression in Fhit-negative highly invasive NCI-H1299 cells by transfection of Fhit cDNA and Fhit inhibition in Fhit-positive poorly invasive HBE4-E6/E7 cells by transfection of Fhit small interfering RNA induce, respectively, a decrease and an increase in migratory/invasive capacities. These changes in cell behavior were associated with a reorganization of tight and adherens junction molecules and a regulation of matrix metalloproteinase and vimentin expression. These results show that Fhit controls the invasive phenotype of lung tumor cells by regulating the expression of genes associated with epithelial-mesenchymal transition. Oncogene (2010) 29, 1203-1213; doi: 10.1038/onc.2009.418; published online 23 November 2009