title: BRG1 targeting STAT3/VEGFC signaling regulates lymphangiogenesis in colorectal cancer.
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.
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jingqin
authors.initials: J
authors.lastname: Lan
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xuelai
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D042583:Lymphangiogenesis / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D042582:Vascular Endothelial Growth Factor C; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: BRG1; STAT3; lymphangiogenesis