Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer.
Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer.
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DOI：
10.1186/1471-2407-13-316
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发表时间：
2013-07-01
期刊：
影响因子：
3.8
通讯作者：
You L
中科院分区：
文献类型：
--
作者：
Bravo DT;Yang YL;Kuchenbecker K;Hung MS;Xu Z;Jablons DM;You L
Wnt-2在癌症中发挥致癌作用，但在肺癌中，哪种Frizzled受体介导Wnt-2信号通路仍不清楚。我们试图（1）鉴定和评估非小细胞肺癌中通过Frizzled-8的Wnt-2信号传导的激活，和（2）测试新型表达构建体显性负性Wnt-2（dnhWnt-2）是否在集落形成测定和异种移植小鼠模型中减少肿瘤生长。采用半定量RT-PCR方法检测50例肺癌组织中Wnt-2和Frizzled-8的表达。TCF报告基因分析（TOP/FOP）用于检测体外Wnt经典途径的激活。设计了一种新的dnhWnt-2构建体，并用于抑制293T、293、A549和A427细胞和异种移植小鼠模型中通过卷曲蛋白-8的Wnt-2信号传导的活化。使用Student t检验进行统计学比较。在50个肺癌样品中，我们鉴定了Wnt-2和Frizzled-8的转录增加之间的91%相关性（p <0.05）。当Wnt-2和Frizzled-8在293T、293、A549和A427细胞中共表达时，Wnt经典途径被激活。当β-catenin存在时，我们使用的dnhWnt-2构建体抑制293 T、293、A549和A427细胞中Wnt-2信号传导的活化，并且减少NSCLC细胞的殖民地形成（p <0.05）。dnhWnt-2构建体对Wnt-2活化的抑制进一步降低了异种移植小鼠模型中肿瘤的大小和质量（p <0.05）。抑制也降低了这些肿瘤中Wnt信号传导的靶基因的表达。我们证明了在NSCLC细胞中通过Frizzled-8受体激活Wnt-2信号传导。一种新的dnhWnt-2构建体显著抑制Wnt-2信号传导，减少体外NSCLC细胞的集落形成和异种移植小鼠模型中的肿瘤生长。dnhWnt-2构建体可能为靶向肺癌中的Wnt通路提供新的治疗途径。
Wnt-2 plays an oncogenic role in cancer, but which Frizzled receptor(s) mediates the Wnt-2 signaling pathway in lung cancer remains unclear. We sought to (1) identify and evaluate the activation of Wnt-2 signaling through Frizzled-8 in non-small cell lung cancer, and (2) test whether a novel expression construct dominant negative Wnt-2 (dnhWnt-2) reduces tumor growth in a colony formation assay and in a xenograft mouse model. Semi-quantitative RT-PCR was used to identify the expression of Wnt-2 and Frizzled-8 in 50 lung cancer tissues from patients. The TCF reporter assay (TOP/FOP) was used to detect the activation of the Wnt canonical pathway in vitro. A novel dnhWnt-2 construct was designed and used to inhibit activation of Wnt-2 signaling through Frizzled-8 in 293T, 293, A549 and A427 cells and in a xenograft mouse model. Statistical comparisons were made using Student’s t-test. Among the 50 lung cancer samples, we identified a 91% correlation between the transcriptional increase of Wnt-2 and Frizzled-8 (p<0.05). The Wnt canonical pathway was activated when both Wnt-2 and Frizzled-8 were co-expressed in 293T, 293, A549 and A427 cells. The dnhWnt-2 construct we used inhibited the activation of Wnt-2 signaling in 293T, 293, A549 and A427 cells, and reduced the colony formation of NSCLC cells when β-catenin was present (p<0.05). Inhibition of Wnt-2 activation by the dnhWnt-2 construct further reduced the size and mass of tumors in the xenograft mouse model (p<0.05). The inhibition also decreased the expression of target genes of Wnt signaling in these tumors. We demonstrated an activation of Wnt-2 signaling via the Frizzled-8 receptor in NSCLC cells. A novel dnhWnt-2 construct significantly inhibits Wnt-2 signaling, reduces colony formation of NSCLC cells in vitro and tumor growth in a xenograft mouse model. The dnhWnt-2 construct may provide a new therapeutic avenue for targeting the Wnt pathway in lung cancer.
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影响因子：
10.5
作者：
Hoppler, S;Brown, JD;Moon, RT
通讯作者：
Moon, RT
影响因子：
4.8
作者：
He, B;You, L;Jablons, DM
通讯作者：
Jablons, DM
DOI：
10.1073/pnas.92.7.3046
发表时间：
1995-03-28
影响因子：
11.1
作者：
MUNEMITSU, S;ALBERT, I;POLAKIS, P
通讯作者：
POLAKIS, P
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
11.2
作者：
Caldwell, GM;Jones, C;Morton, DG
通讯作者：
Morton, DG