title: CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling.
abstract: CEACAM6 is a member of glycosylphosphatidylinositol-linked immunoglobulin superfamily that is implicated in a variety of human cancers. In our previous study, we reported that CEACAM6 was overexpressed in gastric cancer tissues and promoted cancer metastasis. The purpose of this study is to determine the role of CEACAM6 in tumor angiogenesis and mimicry formation. We found that overexpressed CEACAM6 promoted tubule formation dependent on HUVEC cells and vasculogenic mimicry formation of gastric cancer cells; opposing results were achieved in CEACAM6-silenced groups. Moreover, we found that mosaic vessels formed by HUVEC cells and gastric cancer cells were observed in vitro by 3D-culture assay. Overexpressed CEACAM6 in gastric cancer cells promoted tumor growth, VEGF expression and vasculogenic mimicry structures formation in vivo. In accordance with these observations, we found that phosphorylation of FAK and phosphorylation of paxillin were up-regulated in CEACAM6-overexpressing gastric cancer cells, and FAK inhibitor Y15 could reduce tubule and vasculogenic mimicry formation. These findings suggest that CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry formation via FAK signaling in gastric cancer and CEACAM6 may be a new target for cancer anti-vascular treatment.
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Mingde
authors.initials: M
authors.lastname: Zang
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Baogui
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Hexiao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China. Electronic address: byliu@sjtu.edu.cn.
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China. Electronic address: ym10299@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Yan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D058851:GPI-Linked Proteins; D051419:Paxillin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Angiogenesis; CEACAM6; FAK; Gastric cancer; VM