RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer

被引：179

作者：

Li, Qingyuan ^{[1
]}

Lai, Qiuhua ^{[1
]}

He, Chengcheng ^{[1
]}

Fang, Yuxin ^{[1
]}

Yan, Qun ^{[1
]}

Zhang, Yue ^{[1
]}

Wang, Xinke ^{[1
]}

Gu, Chuncai ^{[1
]}

Wang, Yiqing ^{[2
,3
]}

Ye, Liangying ^{[1
]}

Han, Lu ^{[1
]}

Lin, Xin ^{[1
]}

Chen, Junsheng ^{[1
]}

Cai, Jianqun ^{[1
]}

Li, Aimin ^{[1
]}

Liu, Side ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, 1838 Guangzhou Ave North, Guangzhou, Guangdong, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou, Guangdong, Peoples R China

[3] Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Guangdong, Peoples R China

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2019年 / 38卷 / 01期

关键词：

RUNX1; Colorectal cancer; KIT; Wnt/beta-catenin; EMT; TRANSCRIPTION FACTOR; CELL-PROLIFERATION; ENHANCER; COLON; IDENTIFICATION; CONTRIBUTES; REGULATORS; INVASION; FAMILY; KIT;

D O I：

10.1186/s13046-019-1330-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：13

共 44 条

[1] RUNX1 contributes to higher-order chromatin organization and gene regulation in breast cancer cells [J].