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F. Tong



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    Poster Session (ID 8)

    • Event: ACLC 2018
    • Type: Poster Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
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      P096 - MLPH Activates CDC42/PAK1 Signaling to Promote Epithelial (ID 173)

      00:00 - 00:00  |  Author(s): F. Tong

      • Abstract

      Background:
      Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC). Therefore, a better understanding of molecularmechanisms underlying NSCLC development and progression could provide helpful insights for NSCLC prevention and effective treatment. Melanophilin (MLPH) is a protein coding gene encoding a member of the exophilin subfamily of Rab effector proteins. Recently, MLPH was reported to be associated with cancers, however, to date, the role of MLPH in lung cancer has never been studied.


      Method:
      RNA-Sequencing was performed to identify differentially expressed genes- MLPH in lung tissues of NSCLC patients with and without BM, then the expression of MLPH was further examined in the serum of BM+ and BM- patients. To study the role of MLPH in the initiation and progression of NSCLC, we examined MLPH levels in NSCLC cells and tissues and analyzed the relationship between MLPH levels and patient survival. Then we knocked down MLPH in NSCLC cells. We used cell counting kit-8 assay, wound healing assay, transwell assay, flow cytometry analysis, Phalloidin staining, xenografted tumor model and brain metastasis model to determine the effects of MLPH on the proliferation, migration, invasion, EMT, tumorigenesis and brain metastasis of NSCLC. Western blot analysis was used to explore the underlying mechanism.


      Results:
      In this study, we found that MLPH was up-regulated in NSCLC tissues and cells. Patients with high levels of MLPH expression had significantly shorter survival than those with low MLPH expression. In NSCLC cell lines, shRNA-mediated depletion of MLPH inhibited the proliferation, lead to apoptosis, induced G0/G1 arrest and suppressed cell migration, invasion, EMT, tumorigenesis and brain metastasis. Mechanistically, we identified TGF-? as a key downstream effector of MLPH. More importantly, MLPH silencing attenuated CDC42/PAK1 signaling activation at least in part through the downregulation of TGF-?.


      Conclusion:
      Together, our findings demonstrated that MLPH positively modulated the CDC42/PAK1 signaling pathway via TGF-? to promote EMT and metastasis, suggesting MLPH as a potential oncogenic biomarker and a promising therapeutic target in the treatment of NSCLC and brain metastasis.