title: SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Huaxi Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan 610093, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qingnan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Su
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Hanshuo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Huaxi Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan 610093, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Thoracic Oncology, Tumour Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Immunology, Nankai University School of Medicine, Tianjin 300071, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Dechao
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002570:Ceruloplasmin / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C576672:BATF2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; C569485:Batf2 protein, human; D025521:Tumor Suppressor Proteins; D002570:Ceruloplasmin