title: Activating transcription factor 4 promotes angiogenesis of breast cancer through enhanced macrophage recruitment.
abstract: Angiogenesis plays an important role in the progression of tumor. Besides being regulated by tumor cells per se, tumor angiogenesis is also influenced by stromal cells in tumor microenvironment (TME), for example, tumor associated macrophages (TAMs). Activating transcription factor 4 (ATF4), a member of the ATF/CREB family, has been reported to be related to tumor angiogenesis. In this study, we found that exogenous overexpression of ATF4 in mouse breast cancer cells promotes tumor growth via increasing tumor microvascular density. However, ATF4 overexpression failed to increase the expression level of a series of proangiogenic factors including vascular endothelial growth factor A (VEGFA) in tumor cells in this model. Thus, we further investigated the infiltration of proangiogenic macrophages in tumor tissues and found that ATF4-overexpressing tumors could recruit more macrophages via secretion of macrophage colony stimulating factor (M-CSF). Overall, we concluded that exogenous overexpression of ATF4 in breast cancer cells may facilitate the recruitment of macrophages into tumor tissues and promote tumor angiogenesis and tumor growth indirectly.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Chen
authors.identifier: 0000-0002-4236-5476
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Zongjin
authors.identifier: 0000-0002-4603-3743
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Lab of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin 300052, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Xiamen International Travel Healthcare Center, Xiamen 361012, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Tong
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: He
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Sun
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Weijun
authors.identifier: 0000-0002-2836-5445
authors.initials: W
authors.lastname: Su
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C081452:Atf4 protein, mouse; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D051701:Activating Transcription Factor 4; D016173:Macrophage Colony-Stimulating Factor