机构：[1]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.[2]Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China.[3]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100069, China.外科系统普通外科首都医科大学宣武医院[4]Department of Gastrointestinal Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Shanxi Province, China.[5]Internal Medicine‑Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China.[6]Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China.[7]Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China.[8]Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China.[9]Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Ji‑Yan Road, Jinan 250117, Shandong Province, China.[10]Tianjin Medical University, Tianjin 300070, China.
Background Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial-mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation. Methods We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues. Results We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter. Conclusions Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81602578]; Natural Science Foundation of Shandong ProvinceNatural Science Foundation of Shandong Province [ZR2017MH129]; China Pstdoctoral Science Foundation [2017M611177]; Medical Science and Technology Development Plans of Shandong [2015WS0152]
第一作者机构：[1]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
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推荐引用方式(GB/T 7714)：
Xiaodong Yan,Dali Han,Zhiqiang Chen,et al.RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells[J].CANCER CELL INTERNATIONAL.2020,20(1):doi:10.1186/s12935-020-01544-w.
APA：
Xiaodong Yan,Dali Han,Zhiqiang Chen,Chao Han,Wei Dong...&Jie Chai.(2020).RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells.CANCER CELL INTERNATIONAL,20,(1)
MLA：
Xiaodong Yan,et al."RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells".CANCER CELL INTERNATIONAL 20..1(2020)
