Wnt信号通路
生物
转移
癌症研究
转录因子
信号转导
细胞生物学
电池极性
上皮-间质转换
肿瘤进展
连环蛋白
细胞迁移
激活剂(遗传学)
下调和上调
癌变
细胞
癌症
基因
遗传学
作者
Shiping Zhang,Xiaowei Guo,Honggui Wu,Ying Sun,Xianjue Ma,Jikai Li,Qian Xu,Chenxi Wu,Qiwen Li,Cizhong Jiang,Wenzhe Li,Margaret S. Ho,Zhongwei Lv,Lei Xue
出处
期刊:Oncogene
[Springer Nature]
日期:2019-01-25
卷期号:38 (20): 3871-3885
被引量:20
标识
DOI:10.1038/s41388-018-0629-x
摘要
Metastasis begins with a subset of local tumor cells acquiring the potential to invade into surrounding tissues, and remains to be a major obstacle for cancer treatments. More than 90% of cancer patients died from tumor metastasis, instead of primary tumor growth. The canonical Wnt/β-catenin pathway plays essential roles in promoting tumor formation, yet its function in regulating tumor metastasis and the underlying mechanisms remain controversial. Here we employed well-established Drosophila tumor models to investigate the regulating mechanism of Wingless (Wg) pathway in tumor invasion. Our results showed that Wg signaling is necessary and sufficient for cell polarity disruption-induced cell migration and molecular changes reminiscent of epithelial-mesenchymal transition (EMT). Moreover, reducing Wg signaling suppressed lgl−/−/RasV12-induced tumor invasion, and cooperation between Arm and RasV12 is sufficient to induce tumor invasion. Mechanistically, we found that cell polarity disruption activates JNK signaling, which in turn upregulate wg expression through transcription factor activator protein-1 (AP-1). We identified a consensus AP-1 binding site located in the 2nd intron of wg, and confirmed that it is essential for AP-1 induced wg transcription both in vitro and in vivo. Lastly, we confirmed that the transcriptional activation of WNT by AP-1 is conserved in human cancer cells. These evidences reveal a positive role of Wnt/β-catenin pathway in tumor invasion, and provide a conserved mechanism that connects JNK and Wnt signaling in regulating tumor progression.
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