SOX4 activates CXCL12 in hepatocellular carcinoma cells to modulate endothelial cell migration and angiogenesis in vivo

• Published in: Oncogene 2020-06, Vol.39 (24), p.4695-4710
• Main Authors: Tsai, Chi-Neu, Yu, Shu-Chuan, Lee, Chao-Wei, Pang, Jong-Hwei Su, Wu, Chun-Hsin, Lin, Sey-En, Chung, Yi-Hsiu, Tsai, Chia-Lung, Hsieh, Sen-Yung, Yu, Ming-Chin
• Format: Article
• Language: English
• Subjects: 13/106; 13/109; 13/89; 38/89; 59/78; 631/67/1504/1610; 631/67/327; 64/60; 96/1; Angiogenesis; Animals; Apoptosis; Blood clot; Breast cancer; Cancer; Carcinoma, Hepatocellular - blood supply; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell adhesion & migration; Cell Biology; Cell Line, Tumor; Cell migration; Cell Movement; Chemokine CXCL12 - genetics; Chemokine CXCL12 - metabolism; Chemotaxis; Chromatin; CRISPR; CRISPR-Cas Systems; CXCL12 protein; CXCR4 protein; Development and progression; Ectopic expression; Endothelial cells; Endothelium; Hepatocellular carcinoma; Hepatoma; Human Genetics; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - pathology; Humans; Immunoprecipitation; Internal Medicine; Liver cancer; Liver Neoplasms, Experimental - blood supply; Liver Neoplasms, Experimental - genetics; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neovascularization; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Oncology; Oncology, Experimental; Patients; Prognosis; SOXC Transcription Factors - genetics; SOXC Transcription Factors - metabolism; Thrombosis; Thrombosis - genetics; Thrombosis - metabolism; Thrombosis - pathology; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors; Umbilical vein; Vascularization; Xenografts
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-020-1319-z

The overexpression of SOX4 in various kinds of cancer cells was associated with poor prognosis for patients. The role of SOX4 in angiogenesis and tumor microenvironment modulation was recently documented in breast cancer but remains unclear in hepatocellular carcinoma (HCC). In our study, the clinical relevance of SOX4 overexpression in HCC and its role in the tumor microenvironment were investigated. The overexpression of SOX4 (SOX4 high ) in tumor lesions was associated with higher microvessel density ( P  = 0.012), tumor thrombosis formation ( P  = 0.012), distant metastasis ( P