RETRACTED ARTICLE: SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin

• DOI: 10.1038/ncomms11996
• Publication Date: 2016-06-29T10:52:31Z
• Authors: Lei Dai; Xueliang Cui; Xin Zhang; Lin Cheng; Yi Liu; Yang Yang; Ping Fan; Qingnan Wang; Yi Lin; Junfeng Zhang; Chunlei Li; Ying Mao; Qin Wang; Xiaolan Su; Shuang Zhang; Yong Peng; Hanshuo Yang; Xun Hu; Jinliang Yang; Meijuan Huang; Rong Xiang; Dechao Yu; Zongguang Zhou; Yuquan Wei; Hongxin Deng
• Keywords: Mice, Knockout; 0301 basic medicine; Mice, Inbred BALB C; Neovascularization, Pathologic; Science; Tumor Suppressor Proteins; Q; Ceruloplasmin; Neoplasms, Experimental; Article; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Basic-Leucine Zipper Transcription Factors; Cell Line, Tumor; Colonic Neoplasms; Animals; Humans; Female

AbstractSARI, 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.