Down-regulation of NKD1 increases the invasive potential of non-small-cell lung cancer and correlates with a poor prognosis.
Down-regulation of NKD1 increases the invasive potential of non-small-cell lung cancer and correlates with a poor prognosis.
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NKD1 的下调会增加非小细胞肺癌的侵袭潜力，并与不良预后相关。
DOI：
10.1186/1471-2407-11-186
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发表时间：
2011-05-20
期刊：
影响因子：
3.8
通讯作者：
Wang EH
中科院分区：
文献类型：
--
作者：
Zhang S;Wang Y;Dai SD;Wang EH
Naked 1（NKD 1）作为经典Wnt信号通路的负调控因子，在许多正常组织中广泛表达。然而，NKD 1在非小细胞肺癌（NSCLC）患者中的表达模式及其临床病理意义尚不清楚。对35例正常肺组织和100例非小细胞肺癌组织进行免疫组化研究，其中66例有完整随访记录。Western blot和Real-time PCR分别检测NKD 1蛋白和mRNA的表达。为了检测NKD 1对肺癌细胞侵袭能力的影响，通过siRNA下调肺癌细胞系中的NKD 1，然后通过Matrigel侵袭测定来评估侵袭能力。此外，还检测了NKD 1敲低细胞中Dishevelled-1和β-catenin蛋白以及MMP mRNA的表达。在35例新鲜肺癌组织中，27例（79%）NKD 1蛋白表达低于相应的正常组织（P = 0.009）。肺癌组织中NKD 1 mRNA表达水平明显高于癌旁正常肺组织。在100例NSCLC组织中，NKD 1在78例（78%）中的表达显著低于正常组织。NKD 1表达的降低与胃癌的组织学类型（P = 0.003）、分化程度（P = 0.004）、淋巴结转移（P = 0.013）、TNM分期（P = 0.002）和生存期（62.88 ± 3.23 vs 23.61 ± 2.18个月，P = 0.03）有关。此外，NKD 1基因敲低可上调Dishevelled-1和β-catenin蛋白水平，增加MMP-7的转录，增强肺癌细胞的侵袭能力。此外，当用Dishevelled-1抗体处理NKD 1敲减细胞时，它们的侵袭潜力显著降低。NSCLC中NKD 1蛋白减少，但NKD 1 mRNA升高。NKD 1蛋白表达降低与NSCLC预后不良相关。NKD 1可能通过Dishevelled-1抑制经典Wnt通路的活性。
As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression pattern and clinicopathological significance of NKD1 in patients with non-small-cell lung cancer (NSCLC) is still unclear. Immunohistochemical studies were performed on 35 cases of normal lung tissues and 100 cases of NSCLC, including 66 cases with complete follow-up records. The NKD1 protein and mRNA expressions were detected by western blot and Real-time PCR, respectively. To examine the effect of NKD1 on the invasiveness of lung cancer cells, NKD1 was down-regulated by siRNA in lung cancer cell lines and the invasive ability was then evaluated by the Matrigel invasion assay. In addition, the expressions of Dishevelled-1 and β-catenin proteins, as well as MMP mRNA were also examined in NKD1 knockdown cells. In 35 fresh lung cancer tissues examined, 27(79%) of them exhibited lower levels of NKD1 protein in comparison with their corresponding normal tissue (P = 0.009). However, the NKD1 mRNA level was significantly higher in cancerous lung tissues, compared with the adjacent normal tissues. In 100 NSCLC tissues, NKD1 was significantly lower in 78 cases (78%) than in the normal specimens, determined by immunohistochemical staining. The reduced NKD1 expression was correlated with histological type (P = 0.003), poor differentiation (P = 0.004), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and poor survival (62.88 ± 3.23 versus 23.61 ± 2.18 months, P = 0.03). In addition, NKD1 knockdown could up-regulate Dishevelled-1 and β-catenin protein levels, as well as increased MMP-7 transcription and the invasive ability of lung cancer cells. Furthermore, when the NKD1-knockdown cells were treated with Dishevelled-1 antibody, their invasive potential was significantly reduced. NKD1 protein is reduced but NKD1 mRNA is elevated in NSCLC. Reduced NKD1 protein expression correlates with a poor prognosis in NSCLC. NKD1 might inhibit the activity of the canonical Wnt pathway through Dishevelled-1.
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