RUNX1 通过激活结直肠癌中的 Wnt/β-catenin 信号通路和 EMT 促进肿瘤转移。

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

机构信息

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou, Guangdong, People's Republic of China.

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

J Exp Clin Cancer Res. 2019 Aug 1;38(1):334. doi: 10.1186/s13046-019-1330-9.

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/β-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/β-catenin signalling in CRC cells by directly interacting with β-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/β-catenin signalling. Moreover, RUNX1 is regulated by Wnt/β-catenin.

CONCLUSION

Our findings first demonstrate that RUNX1 promotes CRC metastasis by activating the Wnt/β-catenin signalling pathway and EMT.

背景

runt 相关转录因子 1（RUNX1）在上皮肿瘤中发挥癌基因和抑癌基因的作用，异常升高的 RUNX1 被认为有助于结直肠癌（CRC）的发生。然而，其机制尚不清楚。

方法

采用实时定量 PCR 和 Western blot 检测 CRC 和正常组织中 RUNX1 的表达。通过体外和体内功能实验研究 RUNX1 对 CRC 迁移和侵袭的影响。染色质免疫沉淀试验验证了 RUNX1 对 KIT 启动子的直接调控，导致 Wnt/β-catenin 信号通路的激活。

结果

RUNX1 在 CRC 组织中表达上调。上调的 RUNX1 促进 CRC 细胞在体外和体内的迁移和上皮间质转化（EMT）。此外，RUNX1 可以通过与β-catenin 直接相互作用，并靶向 KIT 的启动子和增强子区域来促进 KIT 转录，从而在 CRC 细胞中激活 Wnt/β-catenin 信号通路。这些观察结果表明，RUNX1 的上调是 CRC 标本中的一个常见事件，与癌症转移密切相关，并且 RUNX1 通过激活 Wnt/β-catenin 信号通路促进 CRC 细胞的 EMT。此外，RUNX1 受 Wnt/β-catenin 调控。