Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma.

Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma.
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DOI:
10.1371/journal.pone.0057393
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Pongracz JE
Pongracz JE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bartis D;Csongei V;Weich A;Kiss E;Barko S;Kovacs T;Avdicevic M;D'Souza VK;Rapp J;Kvell K;Jakab L;Nyitrai M;Molnar TF;Thickett DR;Laszlo T;Pongracz JE

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大多数肺癌(LC)属于非小细胞肺癌(NSCLC)类型。两种主要的 NSCLC 亚型,即腺癌 (AC) 和鳞状细胞癌 (SCC),对治疗的反应不同。尽管香烟烟雾与肺癌风险之间的联系已得到充分证实,但在鳞状细胞癌中检测到的非典型 Wnt 通路上调的相关性仍知之甚少。本研究旨在进一步研究 SCC 发育过程中经典和非经典 Wnt 信号传导的分子事件。手术后获得了总共 20 个 SCC 和 AC 样本以及匹配的非癌性对照。 TaqMan 阵列分析证实了 SCC 样本中非经典 Wnt5a 和 Wnt11 的上调,并确定了经典 Wnt 信号传导的下调。在原代小气道上皮细胞(SAEC)和各种肺癌细胞系(例如 A549、H157 等)中测试了分子变化。我们的研究确定 Wnt11 和 Wnt5a 是钙粘蛋白表达的调节因子,并增强 β-连环蛋白向细胞核的重新定位,这是减少细胞粘附的重要步​​骤。所提供的数据确定了 SCC 监管的更多细节,有助于将来识别治疗药物靶点。
The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of β-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future.
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