Down-regulation of NKD1 increases the invasive potential of non-small-cell lung cancer and correlates with a poor prognosis
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- 作者：Sheng Zhang (1)
Yan Wang (1)
Shun-Dong Dai (1)
En-Hua Wang (1) - 刊名：BMC Cancer
- 出版年：2011
- 出版时间：December 2011
- 年：2011
- 卷：11
- 期：1
- 全文大小：3393KB
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23. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/11/186/prepub - 作者单位：Sheng Zhang (1)
Yan Wang (1)
Shun-Dong Dai (1)
En-Hua Wang (1)
1. Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, 110001, Shenyang, China - ISSN：1471-2407
文摘
Background 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. Methods 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. Results 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. Conclusion 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.