Author of

• 25940

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  P2.03 - Biology (Not CME Accredited Session) (ID 952)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26952

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    P2.03-16 - TGF-β Induced EMT and Stemness Characteristics are Associated with Epigenetic Regulation in Lung Cancer (ID 12725)

    16:45 - 18:00  |  Author(s): Nahyeon Kang
    • Abstract

    Background
    

    Transforming growth factor-β (TGF-β) promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT). EMT is often associated with acquisition of stem-like characteristics. In this study, we investigated whether EMT and stem-like characteristics induced by TGF-β could associated with epigenetic regulation in lung cancer.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Human normal epithelial (BEAS-2B) and cancer (A549, H292, H226 and H460) cell lines were incubated with 10 ng/ml of TGF-β for 3 days. Transcriptome analysis of BEAS-2B and A549 cells treated with TGF-β were performed by using next-generation sequencing (HiSeq 2500 system). Western blotting was performed to analyze the expression of epithelial marker (E-cadherin) and mesenchymal markers (N-cadherin, fibronectin, vimentin and α-SMA). Wound healing assay, Matrigel invasion assay, sphere formation assay and in vivo mice tumor model were used to assess functional characteristics of EMT and stemness acquisition. TGF-β induced DNA demethylation was identified by methylation-specific PCR and bisulfite sequencing.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Next-generation sequencing revealed significant changes in the expression of stem cell markers, CD44, CD87 and CD90 in both BEAS-2B and A549 cells. Functional analysis revealed increased wound healing, Matrigel invasion, sphere formation and in vivo mice tumor formation after TGF-β treatment. TGF-β induced EMT was associated with acquisition of stem-like characteristics. CD44, CD87 and CD90 were activated by either TGF-β and treatment with AZA. MSP showed decreased CD44, CD87 and CD90 promoter methylation after TGF-β treatment.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    These results suggest that TGF-β induces stem cell characteristics which are related with CD44, CD87 and CD90 reactivation by promoter demethylation.

    6f8b794f3246b0c1e1780bb4d4d5dc53