Wnt信号通路与非小细胞肺癌发生发展关系的研究进展

doi:10.11904/j.issn.1002-3070.2016.01.014

摘要/Abstract

摘要：

Wnt信号通路参与调控细胞的生长、分化、迁移和凋亡等生理过程,Wnt通路的异常活化与肿瘤的发生、发展密切相关。在非小细胞肺癌(Non-small-cell lung cancer,NSCLC)中,Wnt通路能够调节肿瘤细胞的增殖、黏附、血管生成、侵袭和转移等诸多过程。Wnt通路成员众多,它们的表达水平影响着NSCLC的预后。深入研究Wnt通路与NSCLC发生发展的关系,对于NSCLC的个体化治疗具有指导意义。本文就Wnt通路参与调控NSCLC发生发展的最新进展进行综述。

关键词: Wnt信号通路, 非小细胞肺癌, β连环蛋白, 肿瘤发生, 预后

Abstract:

Wnt signaling pathway participates in the physiological process of cell growth,differentiation,migration and apoptosis.Its abnormal activation is closely related to the tumorigenesis and progression.Wnt signaling is also known to regulate the process of proliferation,angiogenesis,adhesion,invasion and metastasis of tumor cells in non-small-cell lung cancer.There are a lot of members in Wnt signaling pathway and their expression levels affect the prognosis of non-small-cell lung cancer.It plays an instructive role in the individualized treatment of non-small-cell-lung cancer to lucubrate the relation between Wnt signaling pathway and the tumorigenesis and progression of non-small-cell lung cancer.

Key words: Wnt signaling pathway, Non-small-cell lung cancer, β-catenin, Tumorigenesis, Prognosis

中图分类号:

R734.2

王大权综述, 赵路军, 王平审校. Wnt信号通路与非小细胞肺癌发生发展关系的研究进展[J]. 实用肿瘤学杂志, 2016, 30(1): 66-70.

WANG Daquan, ZHAO Lujun, WANG Ping. Research on the progress of the relation between Wnt signaling pathway and the tumorigenesis and progression of non-small-cell lung cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2016, 30(1): 66-70.

参考文献

1 Lundin A,Driscoll B.Lung cancer stem cells:progress and prospects[J].Cancer Lett,2013,338(1):89-93.
2 Stewart DJ.Wnt signaling pathway in non-small cell lung cancer[J].J Natl Cancer Inst,2014,106(1):356-364.
3 García Campelo MR,Alonso Curbera G,Aparicio Gallego G,et al.Stem cell and lung cancer development:blaming the Wnt,Hh and Notch signalling pathway[J].Clin Transl Oncol,2011,13(2):77-83.
4 Togashi Y,Hayashi H,Terashima M,et al.Inhibition of beta-catenin enhances the anticancer effect of irreversible EGFR-TKI in EGFR-mutated non-small-cell lung cancer with a T790M mutation[J].J Thorac Oncol,2015,10(1):93-101.
5 Wang J,Li ZH,White J,et al.Lung cancer stem cells and implications for future therapeutics[J].Cell Biochem Biophys,2014,69(3):389-398.
6 Li XQ,Yang XL,Zhang G,et al.Nuclear beta-catenin accumulation is associated with increased expression of Nanog protein and predicts poor prognosis of non-small cell lung cancer[J].J Transl Med,2013,11:114-125.
7 Reynolds SD,Zemke AC,Giangreco A,et al.Conditional stabilization of beta-catenin expands the pool of lung stem cells[J].Stem Cells,2008,26(5):1337-1346.
8 Pacheco-Pinedo EC,Durham AC,Stewart KM,et al.Wnt/beta-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium[J].J Clin Invest,2011,121(5):1935-1945.
9 Wang G,Wang R,Strulovici-Barel Y,et al.Persistence of smoking-induced dysregulation of miRNA expression in the small airway epithelium despite smoking cessation[J].PLoS One,2015,10(4):e0120824.
10 Whang YM,Jo U,Sung JS,et al.Wnt5a is associated with cigarette smoke-related lung carcinogenesis via protein kinase C[J].PLoS One,2013,8(1):e53012.
11 Xu X,Kim JE,Sun PL,et al.Immunohistochemical demonstration of alteration of beta-catenin during tumor metastasis by different mechanisms according to histology in lung cancer[J].Exp Ther Med,2015,9(2):311-318.
12 Huang CL,Liu D,Ishikawa S,et al.Wnt1 overexpression promotes tumour progression in non-small cell lung cancer[J].Eur J Cancer,2008,44(17):2680-2688.
13 Nakashima N,Huang CL,Liu D,et al.Intratumoral Wnt1 expression affects survivin gene expression in non-small cell lung cancer[J].Int J Oncol,2010,37(3):687-694.
14 王琴,展平,于力克,等.Wnt1在非小细胞肺癌中的表达与预后的关系[J].中国肺癌杂志,2010,(6):586-590.
15 Xu X,Sun PL,Li JZ,et al.Aberrant Wnt1/beta-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery[J].J Thorac Oncol,2011,6(4):716-724.
16 He B,You L,Uematsu K,et al.A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells[J].Neoplasia,2004,6(1):7-14.
17 Lindskog C,Edlund K,Mattsson JS,et al.Immunohistochemistry-based prognostic biomarkers in NSCLC:novel findings on the road to clinical use[J].Expert Rev Mol Diagn,2015,15(4):471-490.
18 Bartis D,Csongei V,Weich A,et al.Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma[J].PLoS One,2013,8(3):e57393.
19 Lu C,Wang X,Zhu H,et al.Over-expression of ROR2 and Wnt5a cooperatively correlates with unfavorable prognosis in patients with non-small cell lung cancer[J].Oncotarget,2015,6(28):24912-24921.
20 胡欣春,徐建军,喻东亮,等.Wnt5a在肺癌A549细胞球增殖和上皮间质转化中的作用及机制研究[J].第三军医大学学报,2014,36(18):1890-1894.
21 Yao L,Sun B,Zhao X,et al.Overexpression of Wnt5a promotes angiogenesis in NSCLC[J].Biomed Res Int,2014,2014:832562.
22 Avasarala S,Van Scoyk M,Wang J,et al.hsa-miR29b,a critical downstream target of non-canonical Wnt signaling,plays an anti-proliferative role in non-small cell lung cancer cells via targeting MDM2 expression[J].Biol Open,2013,2(7):675-685.
23 Tennis MA,Van Scoyk MM,Freeman SV,et al.Sprouty-4 inhibits transformed cell growth,migration and invasion,and epithelial-mesenchymal transition,and is regulated by Wnt7A through PPAR in non-small cell lung cancer[J].Molecular Cancer Research,2010,8(6):833-843.
24 Bikkavilli RK,Avasarala S,Van Scoyk M,et al.Wnt7a is a novel inducer of beta-catenin-independent tumor-suppressive cellular senescence in lung cancer[J].Oncogene,2015.(Epub ahead of print)
25 Kim TH,Moon JY,Kim SH,et al.Clinical significance of aberrant Wnt7a promoter methylation in human non-small cell lung cancer in Koreans[J].J Korean Med Sci,2015,30(2):155-161.
26 Fu Y,Zheng S,An N,et al.beta-catenin as a potential key target for tumor suppression[J].Int J Cancer,2011,129(7):1541-1551.
27 Xiang G,Yi Y,Weiwei H,et al.TGIF1 promoted the growth and migration of cancer cells in nonsmall cell lung cancer[J].Tumour Biol,2015,34(42):5406-5417.
28 程波,权兰菊,杨薇,等.β-catenin核表达与非小细胞肺癌增殖失控和凋亡抑制的关系[J].临床军医杂志,2014,(1):8-13.
29 Miao Y,Wang L,Zhang X,et al.Promoter methylation-mediated silencing of beta-catenin enhances invasiveness of non-small cell lung cancer and predicts adverse prognosis[J].PLoS One,2014,9(11):e112258.
30 杨连赫,王健,张清富,等.Axin基因异常高甲基化对肺癌细胞生物学行为的调节[J].解剖科学进展,2013,(3):263-267.
31 杨连赫,马爽,徐洪涛,等.Axin通过负向调控Wnt通路抑制A549细胞系增殖[J].现代肿瘤医学,2013,21(1):21-24.
32 Yang LH,Xu HT,Li QC,et al.Abnormal hypermethylation and clinicopathological significance of Axin gene in lung cancer[J].Tumour Biol,2013,34(2):749-757.
33 Busch AM,Johnson KC,Stan RV,et al.Evidence for tankyrases as antineoplastic targets in lung cancer[J].BMC Cancer,2013,13:211.
34 Yang Y,Wu J,Cai J,et al.PSAT1 regulates cyclin D1 degradation and sustains proliferation of non-small cell lung cancer cells[J].Int J Cancer,2015,136(4):39-50.
35 Zeng J,Liu D,Qiu Z,et al.GSK3beta overexpression indicates poor prognosis and its inhibition reduces cell proliferation and survival of non-small cell lung cancer cells[J].PLoS One,2014,9(3):e91231.
36 Li S,Qin X,Guo X,et al.Dickkopf-1 is oncogenic and involved in invasive growth in non small cell lung cancer[J].PLoS One,2013,8(12):e84944.
37 Xu H,Wu J,Chen B,et al.Serum Dickkopf-1(DKK1)is significantly lower in patients with lung cancer but is rapidly normalized after treatment[J].Am J Transl Res,2014,6(6):850-856.
38 Salim H,Zong D,Haag P,et al.DKK1 is a potential novel mediator of cisplatin-refractoriness in non-small cell lung cancer cell lines[J].BMC Cancer,2015,15(1):628.
39 Lee SB,Gong YD,Park YI,et al.2,3,6-Trisubstituted quinoxaline derivative,a small molecule inhibitor of the Wnt/beta-catenin signaling pathway,suppresses cell proliferation and enhances radiosensitivity in A549/Wnt2 cells[J].Biochem Biophys Res Commun,2013,431(4):746-752.
40 Xia Y,He Z,Liu B,et al.Downregulation of Meg3 enhances cisplatin resistance of lung cancer cells through activation of the WNT/β-catenin signaling pathway[J].Mol Med Rep,2015,12(3),4530-4537.
41 Wang Z,Ma LJ,Kang Y,et al.Dickkopf-3(Dkk3)induces apoptosis in cisplatin-resistant lung adenocarcinoma cells via the Wnt/beta-catenin pathway[J].Oncol Rep,2015,33(3):1097-1106.
42 Ren J,Wang R,Song H,et al.Secreted frizzled related protein 1 modulates taxane resistance of human lung adenocarcinoma[J].Mol Med,2014,20(1):164-178.
43 Huang C,Ma R,Xu Y,et al.Wnt2 promotes non-small cell lung cancer progression by activating WNT/beta-catenin pathway[J].Am J Cancer Res,2015,5(3):1032-1046.
44 Wang Y,Xia H,Zhuang Z,et al.Axl-altered microRNAs regulate tumorigenicity and gefitinib resistance in lung cancer[J].Cell Death Dis,2014,5(5):e1227.
45 Wang HQ,Xu ML,Ma J,et al.Frizzled-8 as a putative therapeutic target in human lung cancer[J].Biochem Biophys Res Commun,2012,417(1):62-66.
46 Gurney A,Axelrod F,Bond CJ,et al.Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors[J].Proc Natl Acad Sci U S A,2012,109(29).

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