Author of

• 25520

  +

  Poster Display session (Friday) (ID 65)

  • Event: ELCC 2018
  • Type: Poster Display session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1

  • 25238

    +

    8P - Noncanonical Wnt11, a tumor suppressive gene by antagonizing canonical Wnt signaling, represents a putative molecularly therapeutic target in lung cancer (ID 502)

    12:30 - 13:00  |  Author(s): L. Li
    • Abstract

    Background:
    Most studies focused on the role of canonical Wnt signaling pathway, an increasing field of research, however, is concerning about the noncanonical Wnt pathways. The role of Wnt11, a noncanonical Wnt family member, has not been established in lung cancer. Epigenetic inactivation of tumor suppressive genes through promoter CpG methylation is a fundamental regulatory process during tumorigenesis.
    
    Methods:
    The expression levels of Wnt11 were assessed in human normal tissues and lung cancer cell lines panel by semi-quantitative reverse transcription-PCR(RT-PCR). The promoter CpG methylation of Wnt11 were tested in bisulfite treated DNA by methylation-specific PCR (MSP). Western blots assay, colony formation assay, cell proliferation assay, wound-healing assay, dual-luciferase reporter assay and apoptosis assay were used to characterize the changes induced by overexpression of Wnt11.
    
    Results:
    In our study, analysis of Wnt11 expression revealed it was broadly expressed in human normal adult and fetal tissues, while it's frequently downregulated or silenced in multiple lung cancer cell lines. By performing methylation-specific PCR (MSP), promoter CpG methylation of Wnt11 were frequently detected in multiple lung cancer cell lines. Functional assays show that ectopic expression of Wnt11 could suppress tumor cell growth, possibly through inducing apoptosis. Moreover, Wnt11 represses canonical Wnt/β-catenin signaling and AKT signaling pathway. Wnt11 overexpression also reversed EMT and downregulated stem cell markers.
    
    Conclusions:
    Together our data suggest that in lung cancer, Wnt11 is lost by methylation and represents a tumor suppressor by antagonizing canonical Wnt/β-catenin signaling and AKT signaling pathway. Restoration of Wnt11 expression through demethylation could be an important therapeutic approach in the treatment of lung cancer.
    
    Legal entity responsible for the study:
    The Chinese University of Hong Kong
    
    Funding:
    RGC (TBRS #T12-401/13R), China Natural Science Foundation (NSFC #81572327), Johns Hopkins Singapore, and VC special research fund from The Chinese University of Hong Kong
    
    Disclosure:
    The author has declared no conflicts of interest.