RETRACTED ARTICLE: SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin

• Published in: Nature communications Vol. 7; no. 1; pp. 11996 - 15
• Main Authors: Dai, Lei, Cui, Xueliang, Zhang, Xin, Cheng, Lin, Liu, Yi, Yang, Yang, Fan, Ping, Wang, Qingnan, Lin, Yi, Zhang, Junfeng, Li, Chunlei, Mao, Ying, Wang, Qin, Su, Xiaolan, Zhang, Shuang, Peng, Yong, Yang, Hanshuo, Hu, Xun, Yang, Jinliang, Huang, Meijuan, Xiang, Rong, Yu, Dechao, Zhou, Zongguang, Wei, Yuquan, Deng, Hongxin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.06.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 631/443/1338/16; 631/67/1504/1885/1393; 631/80/641/83; 631/80/86; Humanities and Social Sciences; multidisciplinary; Science
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11996

SARI, also called as BATF2, belongs to the BATF family and has been implicated in cancer cell growth inhibition. However, the role and mechanism of SARI in tumour angiogenesis are elusive. Here we demonstrate that SARI deficiency facilitates AOM/DSS-induced colonic tumorigenesis in mice. We show that SARI is a novel inhibitor of colon tumour growth and angiogenesis in mice. Antibody array and HUVEC-related assays indicate that VEGF has an essential role in SARI-controlled inhibition of angiogenesis. Furthermore, Co-IP/PAGE/mass spectrometry indicates that SARI directly targets ceruloplasmin (Cp), and induces protease degradation of Cp, thereby inhibiting the activity of the HIF-1α/VEGF axis. Tissue microarray results indicate that SARI expression inversely correlates with poor clinical outcomes in colon cancer patients. Collectively, our results indicate that SARI is a potential target for therapy by inhibiting angiogenesis through the reduction of VEGF expression and is a prognostic indicator for patients with colon cancer. Ceruloplasmin has an important role in the stabilization and nuclear transport of HIF-1α, thus regulating VEGF expression. Here the authors show that the transcription factor SARI reduces colorectal cancer growth and angiogenesis in vivo by inducing the degradation of ceruloplasmin, thereby inhibiting the HIFα/VEGF axis.