Suppression of lung cancer cell invasion by LKB1 is due to the downregulation of tissue factor and vascular endothelial growth factor, partly dependent on SP1
Suppression of lung cancer cell invasion by LKB1 is due to the downregulation of tissue factor and vascular endothelial growth factor, partly dependent on SP1
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LKB1抑制肺癌细胞侵袭是由于组织因子和血管内皮生长因子的下调，部分依赖于SP1
DOI：
10.3892/ijo.2014.2351
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发表时间：
2014-06-01
影响因子：
5.2
通讯作者：
Nan, Ke-Jun
中科院分区：
文献类型：
--
作者：
Liang, Xuan;Li, Zhao-Lun;Nan, Ke-Jun
LKB 1编码丝氨酸/苏氨酸激酶，通常在许多人类癌症中失活，其介导癌细胞增殖、迁移和分化。最近的研究表明，LKB 1表现出强大的抗转移活性。然而，这种活性的潜在分子机制仍不清楚。在这项研究中，我们将LKB 1重新引入缺乏LKB 1基因的A549肺癌细胞中，以研究LKB 1如何影响肿瘤的侵袭和转移。我们证明了LKB 1蛋白在肺癌细胞中的过表达导致了显著的侵袭抑制。此外，转染肺癌细胞与LKB 1抑制组织因子（TF）和血管内皮生长因子（VEGF）的表达在mRNA和蛋白质水平。在这里，我们提供的证据表明，下调TF和VEGF的LKB 1与细胞侵袭的抑制相关。人肺癌中LKB 1蛋白的过表达与转录因子SP1的活性和表达的降低显著相关。转录因子Sp1的组成性激活在TF和VEGF过表达中起关键作用。我们的结论是，LKB 1通过下调TF和VEGF抑制肺癌细胞的侵袭可能部分依赖于其对转录因子Sp1的抑制作用。总的来说，我们的数据为LKB 1的抗肿瘤活性提供了一种新的分子机制，并可能有助于进一步提高其控制肺癌生长和侵袭的有效性。
LKB1 encodes a serine/threonine kinase generally inactivated in many human cancers, which mediates cancer cell proliferation, migration and differentiation. Recent studies indicated that LKB1 exhibits potent anti-metastatic activity. However, the underlying molecular mechanisms of this activity remain unclear. In this study, we re-introduced LKB1 into A549 lung cancer cells that lack the LKB1 gene to investigate how LKB1 affects tumor invasiveness and metastasis. We demonstrated that overexpression of the LKB1 protein in lung cancer cells resulted in significant inhibition of invasion. Furthermore, transfected lung cancer cells with LKB1 suppressed tissue factor (TF) and vascular endothelial growth factor (VEGF) expression at both the mRNA and protein levels. Here, we provided evidence showing that downregulation of TF and VEGF by LKB1 is correlated well with the inhibition of cell invasion. Overexpression of the LKB1 protein in human lung cancer is significantly associated with a decrease in activity and expression of the transcription factor SP1. Constitutive activation of the transcription factor Sp1 plays a critical role in TF and VEGF overexpression. We conclude that suppression of lung cancer cell invasion by LKB1 through downregulation of TF and VEGF may partly depend on its inhibitory effect on the transcription factor Sp1. Collectively, our data provide a novel molecular mechanism for the antitumor activity of LKB1 and may help further improve its effectiveness in controlling lung cancer growth and invasion.