title: Taspine derivative 12k suppressed A549 cell migration through the Wnt/β-catenin and EphrinB2 signaling pathway.
abstract: 12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells. In addition, 12k repressed the EphrinB2 and its PDZ protein, impairing the VEGFR2 and VEGFR3 expression in A549 cells, as well as inhibited the downstream of VEGFR2 included PI3K/AKT/mTOR and ERK/MAPK signaling pathways. Taken together, our findings revealed that 12k suppressed migration of A549 cells through the Wnt/β-catenin signaling pathway and EphrinB2 related signaling pathway.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Bingling
authors.initials: B
authors.lastname: Dai
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: zhang2008@xjtu.edu.cn.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D036388:Ephrin-B2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D036388:Ephrin-B2; D051176:beta Catenin; C018394:taspine
keywords: 12k; A549 cells; EphrinB2; Wnt signaling