Author of

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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

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    P3.02-017 - Alpha-catulin/ILK signaling axis could a potential therapeutic target for treating NSCLC metastasis (ID 2955)

    09:30 - 09:30  |  Author(s): Y. Chen
    • Abstract

    Background
    Alpha-catulin is a cytoskeletal linker protein. Integrin-linked kinase (ILK) is a serine/threonine protein kinase implicated in cancer cell proliferation, anti-apoptosis, invasion and angiogenesis. Our previous study found that α-catulin is upregulated in lung cancer cells and directly interacted with ILK. Here, we further investigated the effect of α-catulin/ILK interaction in lung cancer metastasis and evaluated whether this interacting axis could be a potential therapeutic target.

    Methods
    Knockdown and overexpression of α-catulin and ILK genes were performed in non-small cell lung cancer (NSCLC) cell lines. Cell invasion and migration assays were done in 24-well Transwell polycarbonate filters coated with or without Matrigel. Spontaneous and experimental metastasis assays were performed in xenograft mice models to determine the effects of α-catulin on lung cancer cell metastasis in vivo. The public NSCLC cohort datasets were used for validation of the expression of α-catulin/ILK associated with patient survival.

    Results
    In the present study, we demonstrated that α-catulin promoted the migration and invasion of NSCLC cells through the ILK/NF-κB/integrin network. α-Catulin directly interacted with ILK, which in turn activated the ILK/Akt/NF-κB signaling pathway. This led to increased expression of the NF-κB downstream genes fibronectin and integrin α~v~β~3~, which sequentially activated NF-κB signaling and resulted in cancer cell migration, invasion and metastasis. The ILK plus CTNNAL1 two-gene signature was even more strongly associated with clinical outcomes of NSCLC patients.

    Conclusion
    Our data suggest that the alpha-catulin/ILK signaling axis is strongly associated with lung cancer cell migration and invasion and correlated with clinical outcome of NSCLC. Thus, this novel signaling axis could be a potential therapeutic target for treating NSCLC metastasis.