title: Expression of semaphorin 6D and its receptor plexin-A1 in gastric cancer and their association with tumor angiogenesis.
abstract: The semaphorin and plexin family of ligands and receptor proteins provides important axon growth and guidance cues required for development. In recent years, studies have expanded their role in the regulation of cardiac morphogenesis and tumorigenesis. However, the mechanism responsible for their role in regulating cancer development and progression has not been clarified. In the present study, semaphorin 6D (Sema6D) and its receptor plexin-A1 were identified to be expressed at high levels in vascular epithelial cells within gastric cancer, and were positively correlated with vascular endothelial growth factor receptor 2 (VEGFR2). These findings verify our hypothesis that Sema6D and plexin-A1 may be closely associated with tumor angiogenesis. Combined with experimental observations in the MGC803 gastric cancer cell line, it was observed that knocking down plexin-A1 signaling led to a decreased expression of VEGFR2 at the messenger RNA and protein levels. Sema6D recognized and activated plexin-A1, which subsequently activated its downstream target, VEGFR2. The activation of VEGFR2 functioned as a positive regulator of tumor angiogenesis. Our data provided an understanding of the complex signaling cascades involved in the angiogenesis-related pathway in tumor cells. In light of our observations, pharmacological interventions targeting Sema6D/plexin-A1/VEGFR2 signaling may potentially be used as a target for the development of novel anti-angiogenic drugs in gastric cancer.
authors.affiliation: Department of Pathology, Chengde Medical College, Chengde, Hebei 067000, P.R. China; Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China; Institute of Basic Medical Sciences, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The 266th Hospital of Chinese People's Liberation Army, Chengde, Hebei 067000, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China; Department of Pharmacology, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Pathology, Chengde Medical College, Chengde, Hebei 067000, P.R. China; Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Shaochen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology, Chengde Medical College, Chengde, Hebei 067000, P.R. China; Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Yatao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Gynecology and Obstetrics, The Central Hospital of Chengde City, Chengde, Hebei 067000, P.R. China.
authors.forename: Xiaoru
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Chengde Medical College, Chengde, Hebei 067000, P.R. China; Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China; Department of General Surgery, The 266th Hospital of Chinese People's Liberation Army, Chengde, Hebei 067000, P.R. China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhao
keywords: VEGFR2; angiogenesis; gastric cancer; plexin-A1; semaphorin 6D