Oncotarget

Research Papers:

BRG1 targeting STAT3/VEGFC signaling regulates lymphangiogenesis in colorectal cancer

Xu Zhu, Li Sun, Jingqin Lan, Linli Xu, Meng Zhang, Xuelai Luo, Jianping Gong, Guihua Wang, Xianglin Yuan, Junbo Hu and Jing Wang _

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Oncotarget. 2016; 7:36501-36509. https://doi.org/10.18632/oncotarget.9038

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Abstract

Xu Zhu1,*, Li Sun2,*, Jingqin Lan1, Linli Xu3, Meng Zhang3, Xuelai Luo1, Jianping Gong1, Guihua Wang1, Xianglin Yuan2, Junbo Hu1, Jing Wang3

1Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

2Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

3Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

*These authors have contributed equally to this work

Correspondence to:

Jing Wang, email: [email protected]

Keywords: BRG1, lymphangiogenesis, STAT3

Received: December 02, 2015    Accepted: April 11, 2016    Published: April 27, 2016

ABSTRACT

Tumor lymphangiogenesis is an important early event in tumorigenesis, one that promotes lymphatic metastasis. BRG1 (also known as SMARCA4) is a central component of the SWI/SNF chromatin-remodeling complex. In a previous work, we have reported that decreased BRG1 could promote colon cancer cell migration and invasion, and that the BRG1 expression level is negatively correlated with lymphatic metastasis. In the current study, we provide a comprehensive analysis of the role of BRG1 during lymphangiogenesis in colorectal cancer. Lymphatic vessels are more abundant in BRG1 low-expression tumors than in BRG1 high-expression tumors. We investigate the process by which BRG1 can promote VEGFC transcription and induce lymphangiogenesis in vivo and in vitro. We show that BRG1 controls lymphangiogenesis by binding to STAT3 and regulating STAT3 activation. We also prove the mechanisms through clinical samples. In summary, our demonstration of the important roles of the BRG1/STAT3/VEGFC in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function.


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