RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer
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RUNX1通过激活结直肠癌Wnt/β-catenin信号通路和EMT促进肿瘤转移
DOI：
10.1186/s13046-019-1330-9
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发表时间：
2019-08-01
影响因子：
11.3
通讯作者：
Liu, Side
中科院分区：
文献类型：
--
作者：
Li, Qingyuan;Lai, Qiuhua;Liu, Side
背景：RUNT相关转录因子1(RUNX1)在上皮性肿瘤中起癌基因和抑癌基因的双重作用，异常升高的RUNX1被认为与结直肠癌的发生有关。方法：采用实时定量聚合酶链式反应和Western blotting方法检测RUNX1在结直肠癌组织和正常组织中的表达。通过体外和体内功能实验，研究RUNX1对结直肠癌侵袭和迁移的影响。染色质免疫沉淀实验证实了RUNX1对试剂盒启动子的直接调控作用，导致Wnt/β-catenin信号的激活。上调的RUNX1在体内外均促进结直肠癌的细胞转移和上皮向间充质转化(EMT)。此外，RUNX1可以通过直接与β-连环蛋白相互作用，靶向KIT的启动子和增强子区域来促进KIT转录，从而激活结肠癌细胞中的Wnt/β-连环蛋白信号。这些观察表明，RUNX1上调是结直肠癌标本中的常见事件，并与肿瘤转移密切相关，RUNX1通过激活Wnt/β-catenin信号促进结直肠癌细胞的EMT。结论：首次证实RUNX1通过激活Wnt/β-catenin信号通路和EMT促进结直肠癌转移。
Background: Runt-related transcription factor 1 (RUNX1) plays the roles of an oncogene and an anti-oncogene in epithelial tumours, and abnormally elevated RUNX1 has been suggested to contribute to the carcinogenesis of colorectal cancer (CRC). However, the mechanism remains unclear.Methods: The expression of RUNX1 in CRC and normal tissues was detected by real-time quantitative PCR and Western blotting. The effect of RUNX1 on CRC migration and invasion was conducted by functional experiments in vitro and in vivo. Chromatin Immunoprecipitation assay verified the direct regulation of RUNX1 on the promoter of the KIT, which leads to the activation of Wnt/beta-catenin signaling.Results: RUNX1 expression is upregulated in CRC tissues. Upregulated RUNX1 promotes cell metastasis and epithelial to mesenchymal transition (EMT) of CRC both in vitro and in vivo. Furthermore, RUNX1 can activate Wnt/beta-catenin signalling in CRC cells by directly interacting with beta-catenin and targeting the promoter and enhancer regions of KIT to promote KIT transcription. These observations demonstrate that RUNX1 upregulation is a common event in CRC specimens and is closely correlated with cancer metastasis and that RUNX1 promotes EMT of CRC cells by activating Wnt/beta-catenin signalling. Moreover, RUNX1 is regulated by Wnt/beta-catenin.Conclusion: Our findings first demonstrate that RUNX1 promotes CRC metastasis by activating the Wnt/beta-catenin signalling pathway and EMT.