Dishevelled‐3 activates p65 to upregulate p120‐catenin transcription via a p38‐dependent pathway in non‐small cell lung cancer
Dishevelled‐3 activates p65 to upregulate p120‐catenin transcription via a p38‐dependent pathway in non‐small cell lung cancer
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DOI：
10.1002/mc.22196
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发表时间：
2015-07
影响因子：
4.6
通讯作者：
Huanyu Zhao;Yue Zhao;G. Jiang;Xiupeng Zhang;Yijun Zhang;Q. Dong;L. Luan;P. Papavassiliou;Endi Wang;E. Wang
中科院分区：
文献类型：
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作者：
Huanyu Zhao;Yue Zhao;G. Jiang;Xiupeng Zhang;Yijun Zhang;Q. Dong;L. Luan;P. Papavassiliou;Endi Wang;E. Wang
Dishevelled-3（Dvl-3）和p120-catenin（p120 ctn）在非小细胞肺癌（NSCLC）中异常表达，与预后不良相关。Dvl-3在NSCLC细胞中上调p120 ctn转录，但机制尚不清楚。在此，我们将Dvl-3 cDNA瞬时转染至NSCLC细胞。Dvl-3转染足以诱导p38信号传导。反过来，Dvl-3诱导p38介导的p65活化，以促进其核转位。用SB 203580（p38抑制剂）或BAY 11 - 7082（IκB-α磷酸化抑制剂）处理抑制Dvl-3诱导的p65活化。结果进一步表明，激活的p65与PAX 2启动子相互作用，增加PAX 2的表达，PAX 2与p120 ctn启动子结合，从而上调p120 ctn基因的转录。此外，Dvl-3转染增强了活性p65与Sp1的结合，从而降低了Sp1与p120 ctn启动子的结合。上述效应与非小细胞肺癌细胞的生物学行为有关。这些发现证实了p38和PAX 2对于Dvl-3诱导的p120 ctn上调是重要的。Dvl-3激活p38 → p65 → PAX 2 → p120 ctn通路，影响NSCLC细胞的生物学行为。© 2014 Wiley Periodicals，Inc.
Dishevelled‐3 (Dvl‐3) and p120‐catenin (p120ctn) have abnormal expression in non‐small cell lung cancer (NSCLC), which is associated with poor prognosis. Dvl‐3 upregulates p120ctn transcription in NSCLC cells, but the mechanism is unknown. Here we transiently transfected Dvl‐3 cDNA to NSCLC cells. Dvl‐3 transfection is sufficient for induction of p38 signaling. In turn, Dvl‐3 induces p38‐mediated activation of the p65 so as to facilitate its nuclear translocation. Treatment with SB203580 (p38 inhibitor) or BAY 11‐7082 (IκB‐α phosphorylation inhibitor) suppresses Dvl‐3 induced activation of p65. The results further show that active p65 interacts with PAX2 promoter to increase the expression of PAX2 and then PAX2 binds to p120ctn promoter so as to upregulate p120ctn gene transcription. Moreover, Dvl‐3 transfection enhanced the binding of active p65 to Sp1 so as to decrease the binding of Sp1 to p120ctn promoter. The above‐mentioned effects are linked to biological behavior of non‐small cell lung cancer cells. These findings confirm that p38 and PAX2 are important for the Dvl‐3 induced upregulation of p120ctn. Dvl‐3 activates a p38 → p65 → PAX2 → p120ctn pathway to affect biological behavior of NSCLC cells. © 2014 Wiley Periodicals, Inc.